Metal–Organic Frameworks as Tunable Sorbents for Food Sample Preparation

Abstract

Trace-level chemical contamination across globalized food supply chains demands efficient, selective, and sustainable sample preparation strategies for reliable analytical monitoring. Metal–organic frameworks (MOFs) are crystalline porous materials constructed from metal nodes and multitopic organic linkers that have recently emerged as engineered sorbents capable of complementing conventional extraction media, particularly in terms of selectivity, surface area, and compatibility with green analytical chemistry principles. This review critically examines the deployment of MOFs and MOF-based composites as sorbents across the full spectrum of food sample preparation formats, including solid-phase extraction (SPE), magnetic SPE (MSPE), dispersive SPE (d-SPE), miniaturized variants (pipette-tip SPE, d-μ-SPE), solid-phase microextraction (SPME), stir bar sorptive extraction (SBSE), and QuEChERS-based cleanup. Distinct from prior overviews focused primarily on materials chemistry, this review adopts a food-analysis perspective with an explicit translational lens, distinguishing analytically mature applications from those still at the proof-of-concept stage. The physicochemical properties that govern MOF performance in food matrices, like framework chemistry (Zr, Al, Cr, Zn, Fe, Ln), pore architecture, surface functionality, and hydrolytic stability, are discussed in relation to the predominant extraction mechanisms operative for key contaminant classes, including pesticides, mycotoxins, veterinary drugs, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFAS), and heavy metals. Representative applications report recoveries typically within 70–120%, LOQs reaching the ng kg^–1 scale, and RSDs below 10%, with sorbent masses of 3–50 mg and elution volumes as low as 200 μL. The greenness of MOF-based approaches is critically evaluated by consolidating qualitative analytical greenness metric for sample preparation (AGREEprep) indicators across representative studies and explicitly addressing the asymmetry between greener extraction steps and the still-conventional synthesis/activation footprint of most reported MOFs. Practical considerations for routine laboratory implementation, including reusability, synthesis scalability, matrix fouling, and regulatory compliance with SANTE guidelines, are critically assessed. Finally, priority research directions are identified, encompassing mechanochemical and deep eutectic solvent-assisted MOF synthesis, food-grade biocompatible MOFs, and integration into online SPE and lab-on-chip platforms, to bridge materials science and routine food safety monitoring.

1. Introduction

Food safety is a top priority worldwide because of the growth of industrial and agricultural practices along with the globalization of the food supply chain. , Ensuring the absence of harmful chemical residues has become a crucial public health necessity rather than just a legal requirement. Due to their widespread presence, long-lasting nature, and ability to accumulate in the environment, chemical contaminants pose a major concern among various chemical hazards. Quantifying these contaminants at ultratrace levels is hindered by the complex nature of food matrices, which comprise water, lipids, proteins, carbohydrates, and pigments such as chlorophyll and carotenoids. In many cases, these food components are coextracted with the target analytes. They may cause interference during instrumental analysis while posing severe matrix effects during MS detection, jeopardizing the accurate quantification of the target analytes. Therefore, the development and validation of advanced, streamlined, and sustainable pretreatment methods for complex food samples are of primary importance.

Recent experimental research on multiple food commodities has shown that changes in MS-induced ionization are analyte- and matrix-dependent and may be very large for certain analyte–matrix combinations. Consequently, these analytical challenges underline the key role of sample preparation in ensuring reliable quantification of the analytes. An effective preparation step should (i) extract and preconcentrate the target analytes and (ii) remove coextracted matrix components to improve the accuracy and robustness of the instrumental analysis. Multiclass validation studies consistently show that analytical performance, including recoveries, detection limits, and measurement uncertainty, is strongly influenced by the efficiency of sample preparation, as inadequate cleanup can result in poor reproducibility and large recovery variability even when using advanced chromatographic–MS platforms.

The current toolbox for food sample preparation encompasses solid-phase extraction (SPE), dispersive and magnetic SPE (d-SPE, MSPE), solvent-minimized microextraction methods (SPME, SBSE), the QuEChERS approach combined with d-SPE cleanup, and an expanding series of miniaturized variantspipette-tip SPE, microextraction by packed sorbents (MEPS), and in-tube SPME. , Despite the widespread adoption of these techniques, each format carries inherent trade-offs that limit its applicability across the full breadth of food contaminant monitoring. , Generic sorbents (C18, PSA, GCB) often lack the chemical specificity required for broad multiclass screening in fatty or pigmented matrices, resulting in inadequate matrix effect removal and poor reproducibility in LC–MS workflows. , Equilibrium-based microextraction formats (SPME, SBSE) reduce solvent consumption but suffer from limited capacity and susceptibility to fouling in lipid-rich samples, whereas miniaturized SPE platforms, while green-compatible, depend critically on sorbents with exceptional surface area and tailored affinity to achieve the enrichment factors needed at regulatory thresholds. ,− Taken together, these persistent selectivity, capacity, and sustainability trade-offs highlight the need for engineered porous sorbents that combine high surface area with chemically tunable pore environments.

Engineered porous sorbents that combine very large accessible surface area with tunable surface chemistry are becoming more popular as a solution to the selectivity, capacity, and matrix-compatibility issues mentioned above. Among these, molecularly imprinted polymers (MIPs), carbon-based nanomaterials, carbon nanotubes, graphene-based materials, and metal–organic frameworks (MOFs) have become particularly prominent. , MOFs are widely used as sorbents in sample preparation for the determination of small organic contaminants. They are crystalline porous networks constructed from metal nodes bridged by multitopic organic linkers; their modular assembly enables the rational control of pore size, topology, and internal surface functionality. − Many MOFs exhibit exceptionally high specific surface areas and well-defined pore architectures compared to conventional porous materials, which directly translates into high sorption capacity and accessible binding sites for small organic contaminants. ,

By varying the linker geometry, length, ratio, and functional groups, the size, shape, and internal surface properties of the MOF can be fine-tuned for specific applications. − Functional groups can be added through linker selection or postsynthetic modification, enabling the rational tuning of interactions, such as π–π bonding, hydrogen bonding, electrostatics, and coordination, thereby enhancing selectivity in complex mixtures. Hydrolytic and chemical stability are crucial for food-related applications. Modern frameworks that use high-valent metal nodes and composite designs show significantly better resistance to hydrolysis and improved performance in water. Ultimately, MOFs meet or exceed the important goals for “green” sample preparation because they have a high capacity to adsorb, enabling a significant reduction in the required sorbent mass; are easily regenerated; and can be made into composite materials (e.g., magnetic composites, coated fibers) and help support solvent savings in smaller volumes when used in combination with other extraction methods. ,

Several reviews have already addressed the application of metal–organic frameworks (MOFs) as adsorbents for the extraction and isolation of specific compounds from food matrices. ,− Nevertheless, recent studies continue to further advance this field by improving understanding of their performance, selectivity, and applicability in complex food systems. Therefore, the present review particularly emphasizes studies published since 2025, while also considering earlier contributions to the field.

Overall, this review focuses on the deployment of MOFs and MOF-based composites as sorbents for the efficient extraction of organic chemical contaminants from food matrices. Specific objectives are (i) to characterize the key physicochemical properties of MOFs relevant to food analysis, such as framework chemistry (Zr, Al, Cr, Zn, etc.), porosity, surface area, and pre/postsynthetic modification strategies. To this end, particular emphasis is given on hydrolytic and chemical stability as critical factors of performance in aqueous food matrices; (ii) to critically investigate the analytical performance of MOF-based sorbents across established extraction approaches; (iii) to evaluate the greenness and practicality of MOF-based approaches for routine food safety laboratories, by addressing solvent savings, sorbent reusability, synthesis scalability, and compliance with current validation guidelines, while identifying priority research directions, including food-grade/biocompatible MOFs, AI-assisted design, and online/integrated platforms that would accelerate their translation into routine practice.

A literature search was conducted using the databases of Scopus, Web of Science, and Google Scholar to identify relevant studies on the application of MOFs in food analysis and extraction processes. The search primarily covered publications from 2025 onward, while earlier studies of significant relevance were selected and included to provide the background and context.

The search was performed using combinations of keywords such as “metal–organic frameworks”, “MOFs”, “food matrices”, “sorbents”, “sample preparation”, “extraction”, “food analysis”, “solid-phase extraction”, “SPE”, “QuEChERS”, “SPME”, and “SBSE”.

Studies were included if they focused on the synthesis, characterization, or application of MOFs for the extraction, isolation, or removal of chemical compounds from food-related matrices. Articles not directly related to food applications as well as studies focusing on the use of MOFs as sensors for compound detection or for microbial inactivation were excluded.

2. Structural Design Principles of MOFs for Food Sample Preparation

MOFs offer enormous surface areas and tunable surface chemistry that are suitable for various food-related applications. In particular, they can be harnessed for the selective detection and preconcentration of trace-level organic contaminants in complex food matrices. ^15,29 For practical use in food analysis, the chemical composition and porosity of the frameworks need to be adapted for hydrolytic and solvent stability, as well as to enable the processing of bulk materials into forms suitable for analytical use. The ability to control the pore dimensions and configurations optimizes the extraction performance. For example, mesopores (2–50 nm) can accommodate larger biotoxins, whereas micropores (<2 nm) can sieve and concentrate small molecules (pesticides or small antibiotics). Additionally, functionality is expanded by composite formats, such as magnetite@MOF core–shell particles, which combine magnetic recovery and MOF selectivity. In addition, stability can be enhanced by material design. Hydrophobic functionalization (e.g., fluorinated or alkyl linkers, or polymer coatings) reduces water uptake. Core–shell architectures (e.g., Fe₃O₄@MOF) protect the MOF core and facilitate magnetic separation without significantly altering its chemistry. Postsynthetic modifications, including PEGylation and the application of silica and carbon coatings, have been shown to improve water resistance in extraction systems. ,,

2.1. Selectivity toward Food Contaminants

The MOF selectivity for food contaminants is based on the physicochemical complementarity between the properties (chemistry and molecular size) of the analyte and the pore environment and surface functional groups of the sorbent. Nonpolar and π-rich contaminants (such as PAHs) are selectively retained in hydrophobic and aromatic/alkylated pore environments by van der Waals forces and π–π stacking interactions, while polar pesticides, mycotoxins, and veterinary drugs are selectively retained by hydrogen bonding, electrostatic interactions, or coordination to Lewis-acidic metal sites (open metal sites) (Figure ). For example, Cr-based amino-functionalized MOFs (MIL-101-NH₂) were modified with acyl and ethyl groups and 3-aminopropyl triethoxysilane (APTES) based fiber coating. According to this study, MIL-101-NH₂–COCH₃ exhibited the highest extraction efficiency for organophosphorus pesticides, owing to the strong interactions between the polar analytes and the acyl-modified MOF. In addition, studies have shown that bimetallic MOFs demonstrate superior adsorption properties compared to their monometallic counterparts. For instance, insertion of cobalt ions in Co/Ca-BTC MOF improved the adsorption of bisphenol A due to the Lewis base properties of the – OH group in its molecule and the Lewis acid center Co in the Co/Ca-BTC MOF.

1.

Schematic diagram of possible mechanisms for adsorptive removal of hazardous materials over MOFs. Reproduced from open-access ref . License Number 6344241325071. Copyright 2014 Elsevier.

MOFs can be designed for specific contaminant groups and matrices by adjusting the pore size (microporous vs mesoporous), adding specific functional groups (−NH₂, – COOH, – SH, long alkyl or fluoroalkyl chains), or preparing composites/coatings (Table ). For example, a thio-functionalized MIL-53­(Fe) was synthesized through a one-pot reaction by mixing 2-mercapto-2-thiazoline with the original MIL-53­(Fe) backbone. The incorporation of sulfur-containing groups increased the adsorption capacity for Pb­(II) and Cd­(II), which was attributed to the presence of two sulfur atoms and one – NH group that enhanced metal binding.

1. Summary of the Predominant Selectivity Mechanisms and the Corresponding MOF Sorbent Selection based on the Physicochemical Properties of Representative Food Contaminants.

analyte class	target examples	predominant mechanism(s)	recommended MOF
nonpolar/π-rich	PAHs, Nitro-PAHs	π–π stacking, hydrophobic partitioning	ZIF-8, fluorinated MOFs
polar pesticides	neonicotinoids, organophosphorus	hydrogen bonding, polar interactions	UiO-66-NH2, Zr-MOFs
bulky toxins	mycotoxins, veterinary drugs	size exclusion, pore-size matching	mesoporous MIL-101, hierarchical composites
cationic compounds	certain dyes, antibiotics	electrostatic attraction	-COOH or –SO3H-modified MOFs
PFAS	PFOA, PFOS, PFHxS, PFNA	fluorophilic interactions	perfluorinated MOFs, fluoro-linker MOFs

Microporous MOFs (pore sizes <2 nm) can separate small molecules and minimize matrix fouling, while mesoporous materials can trap larger toxins such as many mycotoxins and some veterinary drugs. For example, MIL-68­(Al) features 6.0–6.4 Å micropores and 16–17 Å mesopores, creating optimal spatial configurations for antibiotic molecule adsorption. Hydrophobic analytes are effectively trapped in MOFs with nonpolar pore environments and aromatic surfaces, while polar pesticides and many mycotoxins engage MOFs through hydrogen bonding and polar interactions. Surface chemistry engineering (pre- or postsynthetic modification) is a very effective strategy to modulate affinity and selectivity. Amino (−NH₂) and carboxylate (−COOH) functional groups can improve H-bonding and polar interactions, while sulfonic or sulfonate groups can be used to enhance affinity for cationic compounds, thiol groups for soft metal ions, and long alkyl chains or perfluorinated alkylators for hydrophobic and fluorinated organic compounds (PFAS) or PAHs. Fluorinated MOFs have been specifically shown to preconcentrate perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) with high capacity in d-SPE procedures, while fluorination or alkylation approaches are generally more favorable for lipophilic analyte sorption. , Postsynthetic surface coatings of silica, polymers, or polydopamine (PDA), as well as surface molecular imprinting, can introduce selectivity or matrix protection, but each approach needs to be verified, as surface coatings can also affect pore accessibility and recovery.

Apart from baseline design of the framework structure, deliberate incorporation of structural defects like linkerless sites or metallic clusters is an effective approach for the design of pore structure and reactivity of MOFs. , Commonly generated during synthesis through monocarboxylic acid modulators (e.g., acetic or benzoic acid), these defects directly govern the sorbent performance in food sample preparation. Specifically, missing linkers expose coordinatively unsaturated metal sites (e.g., Zr⁴⁺, Fe³⁺) that act as strong Lewis acids, boosting coordinative interactions with polar contaminants like antibiotics, pesticides, and mycotoxins. , Simultaneously, missing-cluster vacancies generate localized mesopores, broadening tight pore apertures and alleviating steric hindrance for bulkier analytes. These vacancies also alter local charge density and surface hydrophobicity, promoting faster intraparticle diffusion and higher extraction recoveries across complex food matrices.

However, the analytical performance of the selected framework must be rigorously validated through recovery, matrix effects, and leaching experiments. Side-by-side comparison studies are still relatively limited in number; hence, application papers that report complete validation data (recoveries, RSDs, LOD/LOQ, reusability cycles) are the best sources of information for selecting MOF chemistry and functionalization for a specific analyte/matrix combination.

Selectivity is often a result of a combination of pore sieving and surface adsorption, and the prevalent process may vary as a function of particle size, defect chemistry, and sample form (powder, monolith, coating). Thus, method validation should encompass (i) spike recovery studies over representative matrices, (ii) evaluation of matrix effects by comparison of solvent versus matrix calibration, and (iii) evaluation of potential metal or linker leaching (ICP–MS or targeted analysis) to ensure that the analyte is not contaminated and that no food safety concerns arise.

2.2. Types and Structural Characteristics of MOFs

Metal–organic frameworks (MOFs) are crystalline materials composed of an inorganic metal center (metal ion or cluster) coordinated to an organic linker (Figure ). This polymeric approach enables the attainment of unprecedented surface areas (>10³–10⁴ m² g^–1 29 and permanent porosity (>50% pore volume). There are many types of MOFs used in sample preparation strategies. Among others, the most widely studied sorbents include the MOF family, the Matériaux de l’Institut Lavoisier (MIL) family, the University of Oslo (UiO) family, the zeolitic imidazolate frameworks (ZIF) family, the Hong Kong University of Science and Technology (HKUST), and isoreticular metal–organic frameworks (IRMOFs) ,, (Figure ).

2.

Schematic classification and key structural characteristics of metal–organic frameworks (MOFs). A part of this figure has been reproduced from the open-access ref , under the terms of the Creative Commons CC BY license. Copyright 2021 Springer Nature Link.

2.3. UiO Family

They consist of ZrO­(OH) clusters and rigid dicarboxylate linkers, resulting in a three-dimensional microporous framework with an octahedral central cavity and eight tetrahedral corner cages. They produce highly crystalline, microporous frameworks (pore openings 0.7–1.0 nm) with a surface area of ∼ 1000–1200 m² g^–1. Most importantly, Zr–O bonds provide the frameworks with outstanding hydrolytic and thermal stability. For example, UiO-66, consisting of Zr clusters and terephthalate (BDC) (Figure ), can survive in water, strong acid or base solutions, and at temperatures of up to ∼ 500 °C. This exceptional water stability is attributed to the strength of the Zr–O bond and a unique geometry that minimizes water penetration and reduces hydrolysis. The stability of the coordination bond can be explained by the Hard–Soft Acid–Base (HSAB) theory, in which the strong coordination between the “hard” Zr⁴⁺ cation and the “hard” oxygen donors of the carboxylate linkers leads to highly robust frameworks. Furthermore, the framework’s surface OH and aromatic groups offer a lot of sites of adsorption (through H-bonding or interactions) for polar organic toxins. Also, amino-functionalized Zr-MOFs (UiO-66-NH₂) provide surface – NH₂ sites that act as hydrogen-bond donors/acceptors and can enhance capture of neonicotinoids and other polar pesticides; practical applications include UiO-66-NH₂ SPE for imidacloprid and thiamethoxam in fruit and juice matrices with excellent recoveries and method validation metrics. ,

3.

Structural details of the UiO-66-type MOF compounds: (top) formation of the MOF from the self-assembly of metal clusters and BCD ligands, showing that each metal cluster (light green) coordinates to 12 other clusters (light blue), leading to an exceptionally robust framework; (bottom) crystal packing arrangement viewed in two distinct directions, revealing the porous features of this family of MOFs. Images prepared from the crystallographic information file obtained from the Cambridge Structural Database with code RUBTAK04. Reproduced from open-access ref , under the terms and conditions of the Creative Commons Attribution (CC BY) license. Copyright 2021 MDPI.

2.4. IRMOF Family

IRMOFs use Zn₄O clusters with carboxylate linkers to achieve very large pore size (≥1.8 nm) and huge surface area, although many (such as MOF-5) are water-soluble. The isoreticular principle means varying the size and nature of a structure without changing its structure topology. MOF-5 uses BDC as an organic ligand coordinating with Zn²⁺ to form a three-dimensional material in octahedral form (Figure ). The specific surface area of MOF-5 is as high as 2900 m² g^–1. Also, IRMOF-3, a Zn-based MOF featuring 2-amino-benzenedicarboxylate ligands, exhibits exceptional adsorption due to its topology, stability, and porosity. Interestingly, this MOF possesses dual functionality. The amino groups form hydrogen bonds with polar matrix interferents, while simultaneously its Zn²⁺-coordinated benzene moieties enable π–π stacking and van der Waals interactions with nonpolar interferents.

4.

Crystal structures of MOF-5 (C, black; Zn, blue; O, red; guest molecule, yellow sphere; and all H atoms have been omitted for clarity). Reproduced from open-access ref under the terms and conditions of the Creative Commons Attribution (CC BY) license under the terms of the Creative Commons Attribution License. Copyright 2014 Academia.

2.5. ZIF Family

ZIFs are Zn²⁺-imidazolate MOFs. A prototype is ZIF-8, Zn with 2-methylimidazolate, with sodalite topology, having large cage-type cavities (∼1.16 nm) with small 0.34 nm windows between cages (Figure ). It has a very large surface area (≈1500–1600 m² g^–1) and exceptional stability: it resists water, strong bases, and high temperatures (up to 550 °C). It has hydrophobic cages with a very high affinity for nonpolar organic molecules. For example, ZIF-8 materials and derived coatings or fibers have been widely used for the extraction of PAHs and nitro-PAHs from aqueous or mixed aqueous–organic samples. This behavior is mainly attributed to hydrophobic partitioning and π–π stacking interactions between the aromatic rings of the analytes and the imidazolate linkers of the framework. High enrichment factors (EFs) and low limits of detection (LODs) for multiring PAHs are obtained using ZIF-8 SPME fibers and hierarchical ZIF-8 composites. These examples demonstrate the effectiveness of hydrophobic pore chemistry and fiber materials in achieving selective capture of lipophilic pollutants in water or oil extracts. In food extractants, it has been used for column-type SPE to extract antibiotic residues (tetracyclines) in milk. The large tetracycline molecules cannot pass through the small 0.34 nm windows; capture must be occurring at the external surfaces. Nevertheless, very high recoveries (70–100%) were obtained. ZIFs, such as ZIF-8, show greater resistance because of their stable Zn–N bonds. Nevertheless, although it is stable in basic conditions up to 550 °C, it is vulnerable to degradation in acidic conditions (pH < 5), which might be a disadvantage in some acidic foods. , Drawbacks of ZIF-8 include its tendency to aggregate and be poorly dispersed; this can be overcome by supporting it on polymers or fibers.

5.

Structural representation of ZIF-8 showing (left) the framework stick diagram, (center) the sodalite (SOD) tiling topology, and (right) the single cage cavity with tetrahedral ZnN₄ coordination nodes (blue polyhedra) and 2-methylimidazolate linkers. The yellow sphere highlights the internal pore cavity (∼1.16 nm). Reproduced from open-access ref . Copyright (2006) National Academy of Sciences, U.S.A.

2.6. HKUST-1

HKUST-1, also known as Cu₃BTC₂, consists of Cu²⁺ paddle-wheel dimers connected by benzene-1,3,5-tricarboxylate (BTC), forming 0.9 nm pore sizes and >1000 m² g^–1 surface area (Figure ). , It demonstrates high thermal stability and low moisture resistance. The key functionality of Cu-BTC arises from the accessible Cu²⁺ and aromatic surfaces, enabling coordination and π-stacking effects on adsorbates. Cu-MOFs have been investigated for their Lewis acidity and ability to target small, polar, and π-rich compounds (e.g., phenolic compounds and dyes). Although less prevalent in food extractants, Cu-BTC represents a family of MOFs that can target aromatic pesticides and drug residues and is applicable in related fields.

6.

Crystal structure of HKUST-1 showing the Cu₂ paddle-wheel secondary building unit and the three-dimensional porous framework formed by benzene-1,3,5-tricarboxylate (BTC) linkers. Reproduced from open-access ref under the terms and conditions of the Creative Commons Attribution (CC BY) license. Copyright 2018 MDPI.

Cu-based MOFs typically exhibit limited hydrolytic stability. This vulnerability arises from the relatively low Cu–O bond strength and the presence of coordinatively unsaturated sites (open metal sites) in the copper paddle-wheel units. Water molecules can act as competing ligands, attacking these metal centers and displacing the carboxylate linkers, leading to rapid framework collapse. Consequently, although Cu-MOFs are valued for their Lewis acidity and π-stacking capabilities, their application in food analysis is generally restricted to nonaqueous extractions or requires robust protective coatings to prevent degradation in moist environments.

2.7. Al-Based MOFs

Aluminum-based metal–organic frameworks (Al-MOFs) provide exceptional physicochemical stability, which is ascribed to the high bond strength of aluminum–oxygen (Al–O) linkages. Al-MOFs, such as MIL-53­(Al) (Figure ) and MIL-101­(Al), use Al³⁺ nodes with benzene dicarboxylate (BDC) linkers. MIL-53­(Al) has one-dimensional 8–9 Å channels and exhibits “breathing” flexibility (narrow and wide pore forms). It offers good chemical stability and π-rich surfaces. MIL-101­(Al) features much larger cages (>2 nm), enabling the capture of larger species (e.g., some toxins or pigments). However, Al-MILs generally have lower surface areas (∼500–1500 m² g^–1) than Zr-MOFs, and their stability depends on synthesis (some require postsynthetic activation to avoid framework collapse in water). Additionally, Al-based MOFs have been successfully applied in food analysis. For example, magnetic Fe₃O₄@MIL-53­(Al) composites have been used for the extraction of multipollutant residues from milk, demonstrating high extraction efficiency and good recoveries. Similarly, Al-MOF-based pipette-tip SPE has been applied for the determination of fluoroquinolone antibiotics in animal-derived food samples, highlighting the suitability of these materials for complex food matrices.

7.

Combination of an infinite octahedral trans-chain metal building unit and a ditopic linker (a) to form the porous 3D structure with 1D rhombic channels (b). Atom colors: C, black; O, red; Al, blue; H atoms are omitted for clarity. Reproduced from open-access ref . License number 1785996–1. Copyright 2019 Royal Society of Chemistry.

Additionally, Al-based MOFs (e.g., MIL-53, MIL-101, and MIL-100) are known to have high stability because of the strong Al–O bonds, although their performance is highly dependent on the synthesis and activation methods used. The stability of MOFs can also be improved by designing them to be hydrophobic on the surface or by using core–shell structures (e.g., Fe₃O₄@MOF). ,

2.8. Cr-Based MOFs

MIL-101­(Cr) stands out among the numerous extensively studied MOFs for the extraction of organic contaminants in food matrices due to its enhanced adsorption efficiency through π–π interactions with aromatic compounds. MIL-101­(Cr) exhibits exceptional porosity, robust physicochemical properties, high chemical stability, and a high specific surface area (∼4100 m² g^–1). However, its adsorption capacity can be significantly enhanced through chemical modification, particularly by introducing functional groups such as −NH₂, which form hydrogen bonds with substances containing oxygen-containing groups. Moreover, MIL-101­(Cr) combined with other functional materials can form composites that offer synergistic effects. Consequently, Liu et al. showed that the combination of polydopamine (PDA) -coated magnetic nanoparticles and amine-functionalized MIL-101­(Cr) (Fe₃O₄@PDA@MIL-101­(Cr)–NH₂) exhibited exceptional performance in extracting tetracyclines from food samples, attributed to its high specific surface area and mesoporous structure, providing abundant active sites for interaction. The adsorption mechanism involves π–π interactions between the target analytes and the benzene rings in the organic framework, as well as hydrogen bonding between the surface amino groups of Fe₃O₄@PDA@MIL-101­(Cr)–NH₂ and the hydroxyl or carbonyl groups of the analytes.

2.9. Ln-Based MOFs

A heterobimetallic La–Sm metal–organic framework (MOF) constructed with 2,5-pyridinedicarboxylic acid (DPA) has been applied as a sorbent in matrix solid-phase dispersion (MSPD) for the extraction of eight pesticide residues from pepper samples (Capsicum annuum). The method provided recoveries ranging from 52.7% to 135% for different herbicides and insecticides, highlighting the applicability of lanthanide-based MOFs for direct sample preparation in complex food matrices. In addition, lanthanide MOFs have also been explored in dairy analysis.

A Dy-MOF-based fluorescent sensing system has been developed for ciprofloxacin detection and successfully applied to cow milk samples, yielding recoveries of approximately 97–110%. Similarly, Dy-MOF/graphene oxide composites have been employed in dispersive solid-phase extraction for the determination of pharmaceutical residues in eggs and milk, further demonstrating the versatility of Ln-MOFs in food safety and contaminant monitoring applications.

2.10. F-Based MOFs

Fluorinated metal–organic frameworks (F-MOFs) are materials in which fluorine is incorporated into the structure through fluorinated metal or semimetal clusters, fluorinated organic linkers, or a combination of both components. Because the covalent C–F bond differs significantly from the more ionic metal–fluorine (M–F) bond in terms of bond length, charge distribution, and dipole moment, materials built from these different units exhibit distinct properties and are suited to a wide range of applications. MOFs built from fluorinated organic linkers are more extensively developed like aromatic fluorinated groups or perfluorinated aliphatic chains.

2.11. Effect of Synthesis and Activation Parameters on the Extraction Performance

The physicochemical properties of MOFs that ultimately govern extraction performance, surface area, pore accessibility, crystallinity, and defect density, are not fixed by chemical composition alone but are strongly dependent on the synthesis route and postsynthetic activation protocol. Reaction temperature, time, solvent identity, and modulator/aging conditions all influence nucleation and growth kinetics, and consequently crystallite size, particle morphology, and the degree of pore blockage by the residual unreacted linker or solvent. The same variables also set the concentration of structural defects and thus the density of coordinatively unsaturated metal sites available for analyte binding (Section ). Activation (solvent exchange and thermal/vacuum treatment to evacuate the pores) is equally critical: incomplete activation leaves guest solvent molecules trapped within the framework, measurably reducing accessible surface area and, in turn, sorption capacity, while excessively harsh activation (high temperature, prolonged vacuum) can induce partial framework collapse or ligand decomposition, particularly in less robust chemistries (Section ). For food-related sorbents, where batch-to-batch reproducibility and scalability are prerequisites for routine use (Section ), the synthesis method also determines whether green alternatives (aqueous, mechanochemical, or microwave-assisted routes) can match the crystallinity and surface area of conventional solvothermal synthesis, a point directly relevant to the greenness assessment in Section . Although systematic synthesis-optimization studies are scarce in the food-application literature, a limited number of within-study paired comparisons compiled in Table do permit a defensible assessment of synthesis–performance relationships. Restricting the analysis to such pairs, in which a single synthesis or fabrication variable was altered while the matrix, analyte panel, spike level, and instrumentation were held constant, avoids the confounding inherent in cross-study comparison, where differences in the calibration strategy, matrix complexity, and detection technique preclude the attribution of performance differences to the material alone. Three of the 24 studies in Table satisfy this criterion. Introducing a second, epitaxial growth step to generate a MOF-on-MOF architecture (Fe/Co-MIL-88A versus Fe/Co-MIL-88A-on-MIL-88B, Entry 14) lowered LODs for organophosphorus pesticides from 0.04–0.09 to 0.02–0.08 ng mL^–1 and improved reusability, at the cost of a more elaborate two-stage synthesis. Incorporation of graphene oxide into a lanthanide framework (Dy-MOF versus Dy-MOF-GO, Entry 12) increased adsorption capacity, recovery, and reusability for pharmaceutical residues in egg and milk without any modification of the parent framework chemistry. Substituting 30% of the terephthalate linker with lauric acid in the synthesis mixture of MIL-53­(Al) (Entry 16) improved bisphenol retention by strengthening hydrophobic pore interactions, indicating that linker stoichiometry, rather than framework identity, governed selectivity in that system. Taken together, these comparisons indicate that postsynthetic architectural and compositional modification, rather than the choice of parent framework, accounts for the largest reported gains in sensitivity and reusability while simultaneously increasing synthesis complexity, with the batch-to-batch reproducibility and greenness consequences discussed in Sections and 4.4. Defect chemistry provides a parallel and mechanistically explicit link: because defect density is itself governed by modulator concentration, temperature, and reaction time (Section ), the open metal sites and enlarged pore apertures that enhance the extraction of polar and bulky food contaminants are a direct and tunable consequence of the synthesis protocol rather than an intrinsic property of the framework. Beyond these three cases, however, none of the food-application studies summarized in Table reports a systematic optimization of synthesis parameters against analytical figures of merit; most adopt a single, literature-reported protocol without examining how deviations in temperature, time, solvent identity, or activation conditions would affect recovery, LOD, or reusability. This constitutes a methodological gap rather than a mere omission: because the paired comparisons above demonstrate that fabrication variables can shift LODs by a factor of 2 within a single study, a single reported protocol cannot be assumed to represent the achievable performance of a given material, and synthesis–performance relationships should therefore be established and reported alongside validation data.

2. Representative Applications of MOF-Based Materials in Sample Preparation for Food Analysis.

entry	MOF material	target analyte	sorbent amount	food matrix	method	LOD	LOQ (μgkg–1)	recovery (%)	RSD (%)	extraction Time	reference
1	SO3–UiO-66	Sulfonamides	-	Precooked foods	SPE-HPLC	0.17–1.27 μg kg–1	2.15–4.98 μg kg–1	96.1–104.8	<8.5	<35 min
		Parabens				0.02–0.12 μg kg–1	0.13–0.46 μg kg–1	95.1–105.5	<7.3
2	Imprinted MOF	Fluoroquinolone	4 mg	Pork	SPE-LC-MS	0.03–0.12 μg kg–1	0.12–0.36 μg kg–1	70.2–113.6	0.3–8.3	30 min
				Milk		0.02–0.12 μg kg–1	0.05–0.40 μg kg–1
3	Al-MOF	Aflatoxins	15 mg	Vegetable oils	SPE-LC-MS/MS	0.06–0.25 μg kg–1	0.21–0.84 μg kg–1	74–110	<11	NR
4	Fe3O4@ZIF-8&F13	PFCAs	5 mg	Milk	MSPE-LC-MS/MS	0.005–0.021 ng g–1	0.017–0.069 ng g–1	95.5–110.2	<4.0	5 min
				Tomato				91.2–114.9
				Fish				88.4–107.1
5	Fe3O4@MOF-APT	Aflatoxin B1	10 mg	Grain samples	MSPE-HPLC–PCD–FLD	0.02 μg kg–1	0.06 μg kg–1	89.7–99.5	1.1–4.5	20 min
6	Fe3O4@PCN-224	OPPs	8 mg	Green, black, and dark tea samples	MSPE-HPLC-UV	0.014–0.051 μg L–1	0.046–0.168 μg L–1	86.16–106.45	0.08–4.96	20 min
7	Fe3O4@ZnAl-LDH@MIL-53(Al)	Triazole fungicides	30 mg	Fresh fruit juices	MSPE-HPLC-UV	0.013–0.030 μg mL–1	0.045–0.100 μg mL–1	73.3–104.3	≤6.8	15 min
8	Zr-MOF@Fe3O4	Pb (II)	40 mg	Water and tea samples	MSPE-FAAS	3.9 μg L–1	13 μg L–	96	<4	20 min
9	Fe3O4@MOF-545-AMSA	HAAs	3 mg	Meat products	MSPE-UPLC -MS/MS	0.1–0.5 μg/kg	0.3–1.0 μg/kg	83.7% and 111.0%	<6	10 min
10	UiO-66- NH2@Fe3O4	UV filters	30 mg	Fish, seafood, and mussel samples	MSPE-GC-MS	0.05–0.5 μg kg–1	7.37 μg L–1	83–107	≤7.1	30 min
11	NiCoMn-MOF	Phthalate esters	15 mg	Fruit juices	d-SPE-GC-FID	0.11–0.5 ng mL–1	0.36–1.0 ng mL–1	65–93	4.9–6.8	10 min
12	Dy-MOF	Drug residues	20 mg	Egg, milk	d-SPE-HPLC-UV	0.02–0.17 μg mL–1	0.05–0.5 μg mL–1	59.39–99.38	1.5–8.5	15 min
	Dy-MOF-GO
13	Na-BiMOF	PFOA	10 mg	Raw cow milk	d-SPE-HPLC–MS/MS	16 ng L–1	53 ng L–1	73	≤4.2	3 min
		PFOS				11 ng L–1	36 ng L–1	78
14	Fe/Co-MIL-88A	OPPs	45–46 mg	Lettuce, tomato, cucumber, white grape and orange juice	D-μ-SPE-GC–MS	0.04–0.09 ng mL–1	0.13–0.30 ng mL–1	93.5–103.6	4.37–6.33	11.5 min
	Fe/Co-MIL-88A-on-MIL-88B					0.02–0.08 ng mL–	0.07–0.27 ng mL–
15	TF-MIL-53(Al)	Insecticides	-	Water, cucumber, and juice samples	PT-μ-SPE-HPLC	0.3–1.5 μg L–1	1.0–5.0 μg L–1	86.0–100.7	1.8–3.3	15 min
16	MIL-53(Al)-BDC/LA (70:30)	Bisphenols	20 mg	Tea and noodles	PT-μ-SPE-HPLC	0.01–0.1 μg L–1	0.04–0.4 μg L–1	82.0–96.4	<7	20 min
17	PSF beads–NH2–MIL- 101(Cr)	Pesticide residues	50 mg	Tea, water, and honey	PT-μ-SPE-HPLC-DAD	0.2–8	NR	82.27–102.91	2.5–5.9	15.13 min
18	Eu-MOF@Fe3O4	Co (II)	10 mg	Peanuts, vegetables, and water samples	μ-SPE	2.21 μg L–1	7.37 μg L–1	81–104	4.1–7	15 s
19	DMOF-1	Pesticides	-	Rice	SPME-GC–FID	1.11–2.10 μg kg–1	-	87–111	10.2–13.6	40 min
20	Co/Ni-MOF@MoS2. CNMMS	HPAHs	-	Domestic water	SPME-GC–MS	0.09–0.64 ng L–1	0.31–2.13 ng L–1	82.2–105	<16	35 min
				Beverage samples				73.5–107	<19
21	β-CD-MOF/CE	Biogenic amines	3 mg	Fresh and canned fish	SPME-GC–MS	0.03–0.11 ng g–1	0.09–0.36 ng g–1	82–90	2.3–4.5	6 min
					SPME-HPLC	0.09–0.15 ng g–1	0.311–0.520 ng g–1		5/2–7/7
22	NH2-UiO-66@NaOA	PAHs	-	Water samples, honey, and black tea	SPME-GC–FID	0.014–0.083 ng mL–1	0.048–0.278 ng mL–1	85.51–108.95	0.21–10.55	40 min
23	MIL-68(Al)	Tetracyclines	0.5 mg	Milk	SBSE-UPLC-DAD	0.1–0.3 ng mL–1	0.4–1.0 ng mL–1	76.7–89.8	3.4–7.2	75 min
				Chicken				77.9–105.5	3.1–8.4
				Egg				102.9–108.2	5.1–8.3
24	IRMOF-3	Pesticides	40 mg	Lonicera Japonica	QuEChERS-GC–MS/MS	0.12–5.58 μg kg–1	0.39–18.61 μg kg–1	77.4–110.4	9.5	1 min

3. MOF-Based Extraction Techniques in Food Analysis

3.1. Solid-Phase Extraction

Solid-phase extraction (SPE) with adsorbent particles such as silica, C18, C8, phenyl, ion-exchange, or polymeric phases is a cornerstone of food sample preparation, offering robust enrichment, well-established protocols, and straightforward coupling to chromatographic detection. Sorbent properties, including particle size, shape, and functionality, are critical for analyzing trace analytes in complex matrices. Especially when used in online configurations, it minimizes sample handling and improves throughput. Its main inherent constraints are the relatively large sorbent masses and elution volumes required compared to miniaturized formats, and the strong dependence on sorbent surface chemistry to achieve adequate selectivity in complex food matrices. Streamlined MOF-based SPE can improve capacity and selectivity per unit sorbent mass through tunable pore environments and functional sites while remaining fully compatible with conventional cartridge and online SPE workflows. MOFs used in SPE are typically packed between porous disks in the column, although this approach requires relatively large amounts of sorbent. Materials from the University of OsloUiO are widely used. For example, the synthesis of sulfonic acid functional MOFs (SO₃–UiO-66) (Entry 1, Table ) starts with an amine-functionalized UiO-66 (NH₂–UiO-66), and then the amino groups are converted to thiols by postsynthetic oxidation. This sorbent was packaged in a steel cartridge and coupled to the online SPE-HPLC system for the simultaneous determination of sulfonamides and parabens in precooked food samples. According to the authors, the proposed method is reliable and sensitive, providing limits of detection at the μg kg^–1 level, while achieving satisfactory recoveries and good repeatability. In another study, the synthesis of an imprinted MOF was described, using pipemidic acid as a dummy template through the in situ development of imprinted cavities within the framework of UiO-66-NH₂ using the molecular imprinting technique (Figure ) for extracting fluoroquinolone antibiotics from pork and milk (Entry 2, Table ). Using the imprinted MOF as an SPE adsorbent, a selective and sensitive analytical method was developed for the quantitation of six fluoroquinolone residues in milk and pork samples using MIP-SPE coupled with LC–MS. This method afforded efficient, selective extraction with satisfactory recoveries, low LODs, and high precision. Also, Jiang et al. reported a novel Al-MOF employed for the efficient adsorption of aflatoxins in vegetable oils, due to the hydrogen bonding and π–π interactions between the active sites within its pores and the target aflatoxins (Entry 3, Table ). Based on this material, an SPE-LC–MS/MS method was developed, providing high recovery rates, low LODs, and excellent accuracy and precision.

8.

Schematic illustration of the preparation of an imprinted MOF. Reproduced from ref . License number 6277250706254. Copyright 2025 Elsevier.

Overall, MOF-based SPE appears analytically mature for the selective enrichment of moderately polar contaminants in food matrices, particularly through online and molecularly imprinted configurations. Yet, the larger sorbent masses inherent to the cartridge format and the limited interlaboratory data on packing reproducibility and batch-to-batch consistency currently constrain its translation to routine use.

3.2. Magnetic Solid-Phase Extraction

Magnetic solid-phase extraction (MSPE) has emerged as an attractive alternative to simplify SPE as the use of an external magnetic field eliminates the stages of centrifugation and filtration while accelerating phase separation and reducing solvent consumption and overall workflow complexity. The absence of centrifugation or filtration makes it simpler and faster than d-SPE, without requiring expensive equipment or large eluent volumes, providing rapid extraction, easy phase separation, low cost, and environmental benefits. Its main inherent constraints are the multistep synthesis required to produce stable magnetic composites, the risk of shell detachment or magnetic core degradation under prolonged or acidic conditions, and the lack of harmonized criteria for reporting reusability and batch-to-batch reproducibility. In this context, MOFs are coupled to Fe₃O₄ cores to combine rapid magnetic recovery with the high surface area, tunable porosity, and selective surface chemistry of the framework, enabling the targeted enrichment of chemically diverse contaminant classes from complex food matrices. Ferroferric oxide nanoparticles or magnetite (Fe₃O₄) are widely employed in the preparation of magnetic materials, thanks to their superior magnetic properties, electronic conductivity, biocompatibility, low cost, availability, and recyclability. , In this approach, magnetic nanoparticles are coated with a sorbent layer, followed by the separation of analyte-tagged nanoparticles from the sample solution using an external magnetic field (Figure a).

9.

(a) Typical magnetic solid-phase extraction (MSPE) and (b) dispersive solid-phase extraction (d-SPE) procedures. Reproduced from open-access ref under the terms and conditions of the Creative Commons Attribution (CC BY) license. Copyright 2019 MDPI.

For example, a fluorinated magnetic MOF (Fe₃O₄@ZIF-8&F13) with multiple binding sites was successfully fabricated via a facile method and applied as a reusable MSPE material coupled with LC–MS/MS for the PFCA extraction in food samples (Entry 4, Table ). This method showed low LODs, good precision, and good reusability (>80% efficiency after six cycles). Additionally, a novel aptamer-grafted MOF-functionalized magnetic adsorbent (Fe₃O₄@MOF-APT) was developed by combining UiO-66-NH₂, Fe₃O₄, and AFB1 aptamer, exhibiting high specificity, strong resistance to matrix interference, and good reusability. Fe₃O₄@MOF-APT was used for aflatoxin B1 (AFB1) quantification using the MSPE-HPLC-PCD–FLD method (Entry 5, Table ). This method achieved a low LOD and demonstrated high robustness, enabling the efficient extraction and separation of AFB1 from peanuts, corn, rice, and wheat.

In another study, Fe₃O₄@PCN-224 was effectively produced by integrating magnetic polydopamine (PDA) with a zirconium-based metal–organic framework (PCN-224) as a desirable adsorbent for organophosphorus pesticide (OPP) adsorption. The Fe₃O₄@PCN-224-based HPLC method exhibited low LODs, excellent accuracy, and precision for the enrichment and detection of OPPs in tea samples. Interestingly, the material exhibited an adsorption capacity of 77.88 mg g^–1 for OPPs attributed to synergistic π–π interactions, covalent and hydrogen bonding, as well as other physical interactions between Fe₃O₄@PCN-224 and the pesticides (Entry 6, Table ). Yang et al. synthesized a Fe₃O₄@ZnAl-LDH@MIL-53­(Al) magnetic composite material by modifying MIL-53­(Al) with ZnAl double layered hydroxide (LDH) after magnetization and used it as an adsorbent in the MSPE process to extract triazole fungicides from freshly squeezed fruit juice (Entry 7, Table ). Moreover, the use of Zr-MOF@Fe₃O₄ for separation and/or preconcentration of Pb (II) has been used as a solid-phase extractor for the preconcentration of Pb (II) from water and tea samples before its determination by flame atomic absorption spectrometry (FAAS) (Entry 8, Table ).

Another simple and efficient MSPE strategy was developed employing Fe₃O₄@MOF-545-AMSA as an adsorbent with Fe₃O₄ as the magnetic core, Zr as the coordination metal ion, tetrakis­(4-carboxyphenyl) porphyrin and benzoic acid as organic ligands, and aminomethanesulfonic acid (AMSA) (Entry 9, Table ). The nanomaterial exhibited a high specific surface area, excellent chemical stability, superparamagnetism, and other characteristics suitable for automated extraction. The combination of MSPE with UPLC–MS/MS resulted in rapid and accurate identification of heterocyclic aromatic amines in meat products, demonstrating high recovery rates and low LODs. Hejji et al. synthesized UiO-66-NH₂@Fe₃O₄ nanocomposites using a straightforward method and applied them to enrich nine organic UV filters from various fish, seafood, and mussel samples using the MSPE-GC–MS approach (Entry 10, Table ). Under optimized conditions, the proposed approach exhibited low LODs, good recoveries, and RSD ≤7.1%.

Overall, MSPE appears to be one of the most analytically mature formats for MOF-based food sample preparation, owing to its operational simplicity and demonstrated compatibility with diverse contaminant classes; nevertheless, the synthesis complexity of the magnetic composites, the heterogeneous reporting of reusability (varying cycle numbers and efficiency thresholds), and the limited evidence of long-term coating stability under realistic food matrix conditions still constrain its routine adoption.

3.3. Dispersive Solid-Phase Extraction

Dispersive solid-phase extraction (d-SPE) offers a fast and low-cost alternative to cartridge SPE by dispersing the sorbent directly into the liquid sample or extract, without any pretreatment steps followed by subsequent centrifugation (Figure b). Thus, it maximizes sorbent–analyte contact area, enables near-instantaneous equilibration, and minimizes sorbent and solvent consumption. As a result, the method is fast and efficient, and because it requires only minimal quantities of the sorbent and solvent, it represents a more sustainable alternative to conventional solid-phase extraction methods. Its main inherent limitations are the need for a postextraction centrifugation or filtration step to recover the sorbent, the typically lower enrichment factors compared with cartridge SPE, and the risk of incomplete particle dispersion or sorbent loss between reuse cycles.

MOFs are particularly well suited to this format because their high surface area sustains substantial extraction capacity at very low sorbent doses, while their tunable pore size and surface chemistry enable size sieving and selective interactions with chemically diverse food contaminants. UiO-66 has been utilized as a d-SPE sorbent for pesticides in vegetables, where it effectively excluded larger matrix compounds by size and showed excellent recoveries. More importantly, UiO-66 has been shown to have more than 20 reuse cycles with almost no decline in performance. Recently, a ternary MOF composite (NiCoMn-MOF) has been used as an efficient sorbent in d-SPE of four common phthalate esters from various plastic-packed fruit juice samples prior to their analysis by gas chromatography-flame ionization detector (GC-FID) (Entry 11, Table ). The presence of multiple elements in the structure provides a large specific area, high porosity, and good adsorption capacity, favoring the extraction of these analytes with high efficiency. The key findings of the study include achieving high recoveries, low LOQs and LODs, and excellent repeatability. In another study, highly efficient and reusable sorbents, dysprosium metal–organic framework (Dy-MOF) and its composite (Dy-MOF-GO), were evaluated for their extraction efficiency of drug residues (sulfaguanidine, paracetamol, and sulfadimidine sodium) from spiked egg and milk samples under optimized d-SPE conditions, followed by HPLC analysis (entry 12, Table ). The results clearly demonstrated the superior extraction efficiency of Dy-MOF-GO over Dy-MOF, displaying enhanced adsorption capacity, superior recoveries, and excellent reusability.

A Na–Bi-MOF was prepared from 1,4-benzenedicarboxylic acid (1,4-BDCA) as the linker and bismuth­(III) salt in the presence of sodium hydroxide through a simple method and was successfully employed as a sorbent in the extraction process (Entry 13, Table ). According to the authors, Na⁺ improves the chemical stability of MOF under harsh conditions. The Bi³⁺ Lewis acid sites and hydrogen-bond interactions from 1,4-BDCA enhance the affinity for organic pollutants, while the bimetallic composition creates a porous structure with diverse pores. This MOF combined with the d-SPE-HPLC–MS/MS method was effective for the quantification of PFOA and PFOS in cow milk with high recoveries, low LODs, and satisfactory repeatability.

Overall, d-SPE with MOFs appears well-aligned with green analytical chemistry principles and supports promising reusability claims in selected studies (e.g., >20 cycles reported for UiO-66); however, the postextraction centrifugation or filtration step partially offsets its workflow-speed advantage over MSPE, and reusability, sorbent recovery between cycles, and matrix-dependent behavior are still reported under heterogeneous, mostly single-laboratory conditions.

3.4. Dispersive Micro-SPE (D-μ-SPE)

Dispersive micro-solid-phase extraction (D-μ-SPE) is the miniaturized counterpart of d-SPE, in which only a few milligrams of sorbent are dispersed in the sample or its extract, providing arguably the strongest alignment with green analytical chemistry principles through minimal sorbent, solvent, and sample consumption. Its main inherent limitations are the lower absolute enrichment factor associated with such small sorbent doses, the heightened sensitivity to weighing and dispersion reproducibility, and the operational difficulty of recovering the sorbent at microscale without analyte loss. MOFs are particularly well-matched to this format because the core MOF provides structural stability and a high surface area, while the shell MOF introduces functional groups that enhance the recognition and adsorption of target analytes, even at very low doses. Also, MOF-on-MOF or composite architectures allow tunable shell selectivity to be combined with the structural stability needed for repeated microscale handling. In this context, two sorbents, Fe/Co-MIL-88A and Fe/Co-MIL-88A-on-MIL-88B, were evaluated using GC–MS combined with D-μ-SPE-GC–MS for OPP determination in vegetable and fruit juice samples (Entry 14, Table ). This study revealed that both sorbents demonstrated acceptable recoveries and precision. However, Fe/Co-MIL-88A-on-MIL-88B demonstrated better reusability, lower LODs, and RSDs for OPP extraction than Fe/Co-MIL-88A. Despite its slightly lower sensitivity, the Fe/Co-MIL-88A represents a more economical option due to its simpler synthesis.

Overall, D-μ-SPE with MOFs offers one of the most attractive greenness profiles among MOF-based food sample preparation formats, particularly through MOF-on-MOF designs that decouple structural stability from surface selectivity; nevertheless, the current evidence base remains thin, and the synthesis complexity, microscale reproducibility, and matrix tolerance of these composite sorbents still need to be demonstrated across analyte classes and laboratories before routine implementation.

3.5. Pipette-Tip Micro-Solid-Phase Extraction (PT-μ-SPE)

Pipette-tip micro solid-phase extraction (PT-μ-SPE) is one of the simplest and most cost-effective miniaturized formats, requiring only a few milligrams of sorbent packed between two filter plugs inside a pipette tip, with the entire extraction completed in a few minutes and without the centrifugation or filtration steps needed in dispersive variants. The procedure is straightforward: typically, two pipette tips are connected to form a small column that can be packed with a sorbent for microextraction. Its main inherent limitations are the manual variability of tip packing, the risk of clogging or backpressure when fine sorbent particles aggregate, the typically limited reusability of the tips themselves, and the lower enrichment factor associated with such small sorbent doses.

MOFs are well matched to this format provided they are deployed in appropriate physical forms, for example, grown on solid supports, immobilized in porous polymer beads, or engineered with controlled particle morphology so that their high surface area and tunable selectivity can be combined with adequate flow behavior and packing reproducibility. A small quantity of the MOF (a few milligrams) is placed between two plugs of deactivated cotton or small filters inside pipette tips (Figure ). The pore size of the filters or the amount of cotton used depends on the particle size and quantity of the MOF, ensuring unobstructed solution flow during extraction. In most cases, the entire extraction process can be completed within a few minutes.

10.

Schematic illustration of fabrication of MOF packing in pipette tips for PT-μ-SPE application. Reproduced from open-access ref under the terms of the Creative Commons CC-BY license. Copyright 2024 Elsevier.

MIL-53­(Al) was directly grown on thin aluminum sheets via a solvothermal method and applied as an adsorbent for the determination of insecticides in water, juice, and cucumber samples (Entry 15, Table ). The approach offers several advantages, including high surface area, low solvent consumption, rapid extraction, and simple operation without clogging or backpressure issues associated with pipette tip-μ-SPE. Validation in water, cucumber, and juice samples showed excellent recoveries with good precision. To enhance the efficiency of MIL-53­(Al), a dual-linker version of the material (MIL-53­(Al)-BDC/LA (70:30) was synthesized by Sami et al., 2026, and used as an adsorbent in PT-μ-SPE for the preconcentration and determination of bisphenols in plastic containers and food samples (Entry 16, Table ). The addition of 30% lauric acid enhanced the adsorbent performance, as its long aliphatic chain can improve pore tunability and strengthen hydrophobic interactions with the largely hydrophobic bisphenol molecules, while the aromatic characteristics of terephthalic acid are critical for π–π interactions between the aromatic rings of bisphenols. In another study, pesticide residues in water, tea, and honey were determined using porous polysulfone (PSF) beads/NH₂-MIL-101­(Cr) as the sorbent (Entry 17, Table ). Polysulfone enhanced analyte adsorption, improved extraction efficiency, reduced backpressure, prevented clogging, allowed easy packing and elution, and enabled reuse. Also, they also minimized MOF agglomeration, shortened extraction time, and maintained stability in water across a wide pH range. The method detected pesticides at 33.0–100.0 μg L^–1 with recoveries of 80.0–102.0%.

Overall, PT-μ-SPE with MOFs appears practically appealing for rapid and low-cost food sample preparation, particularly when MOFs are integrated into polymer-supported or substrate-grown architectures that mitigate clogging and improve packing reproducibility; nevertheless, evidence on tip-to-tip reproducibility, automation compatibility, and the trade-off between sorbent reusability and single-use tip economics remains limited and warrants more systematic evaluation.

3.6. Solid-Phase Microextraction

Solid-phase microextraction (SPME) is a solvent-free, equilibrium-based technique that integrates sampling, extraction, and enrichment in a single step on a sorbent-coated fiber operated in either direct-immersion (DI-SPME) or headspace (HS-SPME) mode, placing it among the formats most well-aligned with green analytical chemistry principles (Figure ). Its main inherent limitations are the nonexhaustive nature of equilibrium extraction with the consequent strong matrix dependence, the lower absolute capacity of thin coatings compared with packed sorbents, the fragility and finite thermal or chemical durability of the coatings, and the susceptibility to fouling in fatty or pigmented food matricesparticularly in direct-immersion mode. MOFs are deployed in this format as fiber coatings or embedded in supporting matrices because their high surface area, tunable porosity, and tailored functional groups enable selective enrichment of specific contaminant classes (e.g., π–π interactions for PAHs and halogenated aromatics, host–guest recognition for polar analytes through CD-MOFs) at very low coating thickness.

11.

Schematic Di-SPME and HS-SPME sampling modes. Reproduced from ref , license number 1786001–1. Copyright 2020 Springer Nature Link.

A robust magnetic MOF based on europium (Eu-MOF@Fe₃O₄) was effectively applied as an SPME sorbent for the determination of trace cobalt in processed nuts, fruits, vegetables, and water samples (Entry 18, Table ). Under optimum settings, the approach demonstrated exceptional analytical performance characterized by rapid analysis, high selectivity, good precision, relatively low detection limits, and low reagent consumption. The LOD and LOQ were 2.21 and 7.37 μg L^–1, respectively, which indicate a 15-fold sensitivity improvement compared to direct FAAS measurements. Alizadeh and co-workers fabricated a novel SPME fiber using DMOF-1 as the coating material, composed of zinc cation, 1,4-benzene dicarboxylic acid (BDC), and (1,4-diazabicyclo [2.2.2] octane) DABCO (Entry 19, Table ). When coupled with GC-FID, this fiber enables efficient extraction and determination of trace pesticides (diazinon and chlorpyrifos) in rice. It maintained stable performance over 70 extraction cycles without significant loss of efficiency. In another study, the combination of bimetallic Co/Ni-MOF and 30% MoS₂ was selected as a strategy to improve adsorption selectivity, adsorption capacity, and stability for detecting traces of 11 halogenated polycyclic aromatic hydrocarbons (HPAHs). Then, the resulting CNMMS was fixed on the stainless-steel wire (SSW) in 15 s to prepare the SPME fiber for the extraction of trace HPAHs in environmental water, fruit drinks, tea, and beers. The material displayed high crystallinity, strong water and thermal stability (≥265 °C), and a large surface area. According to the authors, the conjugated aromatic framework of the Co/Ni-MOF, derived from 2,5-dihydroxyterephthalic acid as a linker, promotes strong π–π interactions with HPAHs, enhancing analyte affinity and improving the extraction efficiency of the CNMMS-SPME fiber (Entry 20, Table ).

In addition, the flexible structure of cyclodextrins makes them ideal complexation agents for creating metal–organic frameworks (CD-MOFs) and suitable for use as adsorbents in food applications. Thus, another study focused on developing novel β-CD-MOFs/CE electrospun nanofibers to serve as SPME biosorbents for extracting and determining biogenic amines in fresh and canned fish (Entry 21, Table ). This study highlights the advantages of MOFs and β-CDs in selectively adsorbing target analytes, thereby enhancing food contamination detection. Under optimized conditions, the prepared biosorbent exhibited high repeatability, accuracy, efficiency, and low LODs for the determination of biogenic amines in real samples. Chen et al. developed the NH₂–UiO-66@NaOA composites with high surface area and strong hydrophobicity, which were used as SPME coatings on stainless-steel wire for the GC-FID analysis of PAHs in water samples, honey, and black tea (Entry 22, Table ). The method showed low LODs and good reproducibility with high extraction efficiency attributed to the porous structure and π–π hydrophobic interactions with PAHs.

Overall, MOF-based SPME shows clear analytical promise for specific contaminant classes, namely, PAHs, halogenated aromatics, biogenic amines, and trace metals, and benefits from the diversity of supports onto which MOF coatings can be immobilized (stainless-steel wire, electrospun nanofibers, magnetic substrates); nevertheless, fiber-to-fiber reproducibility, coating durability under repeated thermal desorption, and the very limited number of cross-study direct comparisons (most reports rely on custom-made, single-laboratory fibers) currently restrict the generalizability of the reported performance figures.

3.7. Stir Bar Sorptive Extraction

Although stir bar sorptive extraction (SBSE) operates on principles closely related to SPME, it employs a substantially larger sorptive phase coated onto a magnetic stir bar, resulting in higher capacity, a larger phase ratio, and consequently improved preconcentration efficiency for trace contaminants. Recent reviews have emphasized that SBSE has become an increasingly important tool in food analysis because of its simplicity, sensitivity, and compatibility with chromatographic platforms; − however, conventional SBSE is still often constrained by the limited polarity range of classical PDMS (polydimethylsiloxane) coatings, which makes it more suitable for nonfatty matrices and nonpolar or semipolar analytes. Its main inherent limitations are the polarity range traditionally restricted by classical PDMS coating chemistry, the mechanical and chemical durability of the coating under prolonged stirring and solvent contact, the limited number of commercial coatings (with most advanced applications relying on custom-prepared bars), and the typically longer equilibration times relative to dispersive formats.

MOF-based sorbents have been introduced to overcome these limitations, taking advantage of the high surface area, tunable pore structure, and chemical versatility of MOFs. Recent studies reported the use of metal–organic framework-embedded polyHIPE monolithic composites in magnetic stir cake sorptive extraction for tetracycline antibiotics in food samples, representing an early example of MOF-assisted sorptive extraction in this field. More recently, MOF-functionalized SBSE platforms have shown clear progress in real food matrices: MIL-68­(Al)-coated frosted glass rods were applied in SBSE-UHPLC for tetracycline determination in milk, chicken, and egg samples, with recoveries of 75.2–115.1% (Entry 23, Table ). Together, these studies indicate that MOF-based SBSE systems are expanding the applicability of sorptive extraction toward more challenging food matrices and improving sensitivity, selectivity, and robustness.

Overall, MOF-based SBSE remains at an earlier stage of development than the MSPE, d-SPE, or SPME formats discussed above, with only a small number of food applications reported to date; the recoveries obtained in selected studies (e.g., MIL-68­(Al)-coated frosted glass rods for tetracyclines in milk, chicken, and egg) suggest analytical promise, but the long-term mechanical durability of the coatings under stirring, bar-to-bar reproducibility, and direct benchmarking against optimized PDMS-based SBSE methods all require systematic evaluation before MOF-based SBSE can be considered analytically mature for routine food analysis.

3.8. QuEChERS Approach

The Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) protocol is the dominant routine sample-preparation approach in modern food contaminant monitoring, owing to its multiresidue capability, low solvent consumption, operational simplicity, and full compatibility with chromatographic-MS detection. Over the past two decades, QuEChERS has been extensively implemented for the extraction and cleanup of pesticides, veterinary drugs, and emerging contaminants in a wide range of food matrices, including fruits, vegetables, cereals, dairy products, meat, and processed foods. Its principal inherent limitations lie in the d-SPE cleanup step, where conventional sorbents (PSA, C18, GCB) provide effective but only moderately selective matrix removal: PSA can coretain acidic analytes, GCB strongly adsorbs planar pesticides, and none of these sorbents fully addresses the persistent matrix effects observed in fatty, pigmented, or highly proteinaceous matrices.

However, there have been considerable advancements made in recent years regarding the use of QuEChERS for improved performance, especially in relation to the introduction of new sorbents and cleanup methods. , MOFs are introduced into the QuEChERS workflow specifically as alternative or complementary d-SPE cleanup sorbents, leveraging their tunable pore chemistry and surface functionality to selectively trap matrix interferents while preserving analyte recovery. More specifically, MOFs, which are known to be an extremely promising class of materials owing to their high surface area, modifiable porosity, and surface chemistry properties, lead to effective removal of interference from the sample matrices while obtaining high recoveries of analytes. This has proven extremely useful when analyzing food safety samples, whose complex matrices usually call for selective cleanup methods. For example, MOF-assisted QuEChERS techniques have already found application in the determination of multiple classes of pesticides in herb-based food products like Lonicera japonica. In such techniques, IRMOF-3 has been used as the dispersive solid-phase cleanup agent in the QuEChERS procedure before GC–MS/MS analysis (Entry 24, Table ). The introduction of MOF-based materials into the QuEChERS procedure increased the ability to remove the matrix effect, which gave rise to good separation, high recovery, and excellent precision.

Overall, MOF-assisted QuEChERS appears most realistically positioned not as a wholesale replacement for the well-established PSA/C18/GCB cleanup sorbents  which benefit from full commercial availability, established validation within regulatory food-safety frameworks (e.g., SANTE), and decades of interlaboratory data  but rather as niche, complementary cleanup materials for specific challenging matrix–analyte combinations where conventional sorbents underperform; the available evidence base remains limited to mostly single-laboratory proof-of-concept studies, and the greenness gain achieved at the cleanup step needs to be weighed against the energy and solvent demands of MOF synthesis and activation before a fully favorable net assessment can be made.

4. Green Aspects and Practical Applicability of MOFs in Food Sample Preparation

4.1. Green Advantages of MOF-Based Sorbents

It is important to note from the outset that the green credentials discussed in this section pertain specifically to the extraction/application step; the greenness of MOF synthesis itself, which is often energy- and solvent-intensive, is addressed separately and critically in Section . Green Sample Preparation (GSP) achieves greenness in sample preparation and minimizes the impact on the environment and human health by setting guidelines on aspects dealing with solvents/reagents, materials, waste, energy demand, speed, miniaturization, procedure simplification/automation, and operator safety. The greenness of MOF-based extraction methods is increasingly quantified using standardized tools rather than qualitatively described (Figure ).

12.

Considerations when preparing a MOF for analytical chemistry applications. Reproduced from open-access ref , under the terms and conditions of the Creative Commons Attribution (CC BY) license. Copyright 2019 MDPI.

Considering the rapid expansion of the analytical chemistry field of MOFs, it is important to consider that these and future analytical MOF-based methods must be incorporated into green analytical chemistry (GAC). From this perspective, environmentally friendly methods based on MOFs should include (partially or completely) the following aspects: green design and synthesis of MOFs, evaluation of toxicity issues of MOFs, and incorporation of MOFs in GAC methods.

The development of greener and more sustainable MOFs requires careful selection of both metal nodes and organic linkers. Low-toxicity and abundant metals (e.g., Mg, Ca, Fe, Al, Ti, and Zr) are preferred to minimize environmental risks and reduce costs, particularly for large-scale applications. Considering the organic linkers, readily available and low-cost carboxylic acid linkers are favored over complex ligands that require multistep synthetic reactions with intermediates and byproducts. The greenness of MOF synthesis also depends on the energy input and the solvent choice. Recent efforts have focused on environmentally friendly alternatives to solvothermal methods with high yields, which implies the use of water instead of organic solvents.

AGREEprep evaluates ten impact categories including solvents, materials, waste, energy, sample size, and throughput; GAPI (recently reported as ComplexGAPI) was sometimes preferred for its detailed scoring system. A method with a score above 75 points was classified as green. For instance, a recent milk microextraction study reported an AGREEprep score of 0.71, illustrating numerical substantiation of greenness claims. , According to the AGREEprep evaluation, the method developed by Javanmardi et al. (2023) obtained a score of 0.62, owing to the avoidance of toxic reagents, the use of small sample quantities, and safe operating conditions for the analyst.

With respect to GAC, MOFs appear most compelling when used in a miniaturized form. In light of recent reviews of methods for food sample preparation, μ-SPE typically involves less than 500 mg of the sorbent, whereas in D-μ-SPE, even just several mg of the sorbent is sufficient; for representative applications of MOFs in food analysis, sorbents used included 10 mg of MIL-125-NH₂ in pomelo d-SPE, 4 mg of PCN-222/MOF-545 in pipette-tip SPE, and 5 mg of UiO-66 nanofibers filled into a 200 μL pipette tip. Also, elution volumes for MOF-based sample preparation are greatly decreased in miniaturized methods, as shown in pipette-tip SPEs, with elution volumes varying in size between 200 and 600 μL, whereas those elution volumes in less miniaturized methods remain on the milliliter level (e.g., 3.5–7.8 mL). Thus, the green benefit of MOFs appears to lie not only in their adsorption capacity but also in their practical implementation. ,

Increasing attention has been focused on the development of sorbents that align with the principles of GACs. In cases where the applications involve food, a design-for-benign approach seems to be adopted by designing food-contact MOFs using ligands and ions from nature that are edible and biocompatible. A 2023 review discussed MOFs used in food contact applications, and cyclodextrin-based MOFs were cited as nontoxic, edible structures made up of naturally occurring cyclodextrin and alkali metal ions. For review purposes, such structures would be best explained as a way forward for reducing the issue of toxicity while maintaining the porosity and tunability. ,

4.2. Practical Applicability in Routine Food Analysis

The usefulness of MOFs in food sample cleanup cannot be assessed based on adsorption capacity alone but rather on their robustness in terms of analytical performance, tolerance to complexity, and suitability for integration into a workflow appropriate for routine laboratory settings. Current reviews highlight the need to assess the physicochemical characteristics of the target analytes and MOF, as well as matrix effects, along with the feasibility of incorporating the MOF in the selected micro­(extraction) technique, as the main factors determining the potential of the developed method to become routine. ,

In food analysis, this translation is already visible in several matrix-specific applications. UiO-66-OH was used as an SPME sorbent for trace polybrominated diphenyl ethers in milk, giving recoveries of 74.7–118.0%, relative standard deviations of 7.58–9.48%, and subng L^–1 detection limits, which shows that well-designed Zr-MOF coatings can operate effectively in complex dairy matrices. Similarly, an in-tube SPME setup containing ZIF-8@monolith provided the HPLC-FLD analysis of fluoroquinolones in water and honey, yielding recoveries of 80.1%–119%, RSDs less than 10%, highly sensitive ng L^–1 LODs, and the practicality of semiautomation, alongside low solvent and sample volumes.

Similar evidence is available for dispersive and cartridge-like food-processing workflows. A composite MOF d-SPE method for tetracyclines in honey was reported as effective in a complex food matrix, while a reusable Al-based MOF used for aflatoxin purification in vegetable oils retained 72% adsorption efficiency after eight reuse cycles and delivered recoveries of 74–110% with CV values below 11%. According to the authors, this method achieved superior recovery rates and lower LOD, compared to other non-MOF-based approaches, likely due to the high specific surface area of the Al-MOF material. These examples are important because they show that MOF sorbents can support not only high analytical performance but also reuse and method robustness under food-relevant conditions. ,

Overall, MOF-based sorbents demonstrate strong applicability in routine food analysis, delivering high performance in complex matrices with significantly reduced material requirements compared to conventional sorbents. For example, dispersive μ-SPE and pipette-tip SPE methods typically achieve recoveries of 75–120%, LODs at μg L^–1–ng L^–1 levels, and RSDs <10% using only 5–20 mg of the sorbent and ≤200 μL of the solvent, compared to conventional SPE requiring ∼ 500 mg of the sorbent and several mL of the solvent. , In addition, MOF composites (e.g., magnetic or monolithic formats) enable rapid extraction (often <5 min), simple phase separation, and reusability over ≥5 cycles with >70% efficiency retention, supporting their integration into LC–MS/GC–MS workflows and high-throughput routine analyses. ,

4.3. Current Limitations and Challenges

It should be clarified that hydrolytic instability, discussed below as a key translational challenge, is not evenly distributed across MOF chemistries: as detailed in Section , Zr-based (UiO-66, UiO-66-NH₂) and Zn-imidazolate (ZIF-8) frameworks already display high water, acid, and base stability, whereas Cu-paddlewheel MOFs (HKUST-1) and unmodified Zn₄O-based IRMOFs remain vulnerable to hydrolysis. The challenge identified here therefore concerns (i) the continued reliance on less water-stable chemistries in some reported applications and (ii) the need for systematic long-term (rather than short-term immersion) stability data even for the more robust families under realistic, matrix-aged food-analysis conditions. Although MOF sorbents possess superior analytical properties, there are several challenges associated with their use for food analysis. The most prominent one among others is hydrolytic stability, as the sorbent should maintain its integrity and porous structure during use in aqueous media. However, recent studies have revealed that the interaction between MOFs and water results in either transformation to a stable form or degradation of the framework, depending on the particular process route. Moreover, in foods, the issue becomes even more serious due to the matrix effect and fouling, which have been emphasized in recent reviews of MOFs used in sampling. Another limitation is their scalability and reproducibility. Although greener routes are being developed, current reviews still emphasize the need for more economical and processable MOF syntheses, including the use of water or ethanol as reaction media, solvent minimization, and continuous manufacturing approaches. , Finally, safety-related concerns cannot be ignored in food-facing applications because the potential migration or release of MOF components remains a recognized issue in the broader food-related-MOF literature, including the leaching of metal ions and dissociation of organic linkers.

A further limitation, largely unaddressed in the current literature, concerns competitive adsorption in true multiclass, multiresidue scenarios. Most validated MOF-based methods summarized in Table target a single analyte class (e.g., PFCAs, aflatoxins, tetracyclines) or, at most, a small number of structurally related compounds: of the 24 studies compiled, twenty-two address a single contaminant class or a narrow panel of structural analogues, the largest such panel comprising 11 halogenated PAHs (Entry 20); only Entry 1 combines two chemically distinct classes (sulfonamides and parabens), while Entry 24, although spanning several pesticide subclasses, remains within a single contaminant category. No compiled study simultaneously determines pesticides, veterinary drugs, and mycotoxins. This contrasts sharply with routine regulatory practice, in which multiresidue protocols based on citrate-buffered QuEChERS extraction (EN 15662) are expected to cover hundreds of analytes of widely differing polarity, acidity, and molecular size within a single run.

The nature of this competition warrants precise framing, since a simple mass-balance consideration might suggest it is negligible: at the sorbent masses and analyte levels reported in Table (typically 3–50 mg of the sorbent against analytes at ng kg^–1 to low μg kg^–1 concentrations), the available pool of binding sites exceeds the molar quantity of target analytes by many orders of magnitude, and analyte–analyte competition alone is therefore unlikely to be thermodynamically limiting for frameworks bearing a high density of nonspecific sites. The competition that matters in food analysis is of two other kinds. First, coextracted matrix constituentslipids, sugars, pigments, peptides, and organic acids present at mg g^–1 levels, 6 to 9 orders of magnitude above the analytesoccupy the same open metal sites, functionalized pore walls, and hydrophobic pore volume, so that the effective, matrix-loaded capacity of a sorbent may bear little relation to the capacity determined from single-analyte isotherms in the clean solvent. Second, in materials whose selectivity derives from a low density of highly specific recognition elements, imprinted cavities (Entry 2) or grafted aptamers (Entry 5), the finite-site argument becomes operative even at trace analyte levels, and the affinity-driven selectivity that benefits a single target class in isolation may translate directly into suppressed recovery for lower-affinity co-occurring analytes.

Each of these mechanisms has been characterized quantitatively for porous sorbents, although almost exclusively outside the food-analysis context, and the available evidence argues against extrapolation from single-component data on three distinct grounds. First, for binary polar–apolar mixtures on a structurally and chemically heterogeneous framework, standard ideal adsorbed solution theory (IAST) fails, with agreement recovered only when isotherms are allocated to the individual cage subunits, each exhibiting a pronounced polar or nonpolar adsorptive preference. Sorption capacity within a single framework is therefore not one quantity but a distribution over chemically distinct microenvironments, and the competitive outcome for a diverse analyte panel cannot be predicted from unary isotherms, which is precisely the basis on which the great majority of the sorbents in Table were characterized. Second, competition in multianalyte aqueous systems is not limited to a reduction in uptake but extends to active displacement: in a nine-component micropollutant mixture on activated carbon cloth, coadsorbates of lower adsorption free energy were desorbed from the surface by more strongly retained competitors, alongside sieving effects governed by relative molecular volume. Translated to sample preparation, this means that analytes already retained on the sorbent may be released during the loading of a complex extract, a failure mode invisible to single-analyte validation. Third, competition is not confined to chemically dissimilar analytes: within the PFAS class alone, binary competition between short- and long-chain congeners is measurable and is systematically overestimated by IAST-based models fitted to single-solute data, a finding directly relevant to the two PFAS methods compiled here (Entries 4 and 13), both validated as single-class panels.

Closing this gap requires two deliberately designed experiments that are currently absent in the field. The first is a competitive-binding study in which the recovery of a target analyte is determined in the presence of increasing concentrations of chemically dissimilar coanalytes at concentration ratios reflecting realistic maximum residue limits, yielding competitive rather than single-component isotherms. The second, and analytically more consequential, is a paired determination of recovery in a real matrix extract versus a solvent standard at an identical sorbent-mass-to-total-load ratio, which isolates the contribution of matrix coextractives from that of the analytes themselves. Until such data are reported, MOF-based sorbents should be regarded as validated for the specific, narrow analyte panels in which they were characterized and not for true multiresidue routine screening.

Beyond the specific limitations discussed above, it is important to note that the performance figures compiled in this review are not uniformly favorable, and a genuinely critical reading of the literature must acknowledge their heterogeneity. Recoveries reported across studies span a considerably wider range than the headline 70–120% figure typically emphasized: for example, matrix solid-phase dispersion using a La–Sm MOF for pesticide residues in pepper reported recoveries as low as 52.7% and as high as 135% depending on the analyte, and dispersive SPE using Dy-MOF for drug residues in egg and milk reported recoveries as low as 59.4% (Table ). Furthermore, direct, side-by-side comparisons between MOF-based sorbents and conventional sorbents (PSA, C18, GCB, and generic silica) under strictly identical matrix, spike level, and instrumental conditions remain rare; most reported advantages are inferred by comparison with historical literature values rather than concurrent benchmarking. Reusability claims are similarly heterogeneous, with cycle numbers ranging from six to more than 20 and efficiency retention thresholds defined inconsistently across studies, which precludes a quantitative cross-study synthesis of sorbent durability. These inconsistencies, together with the synthesis-extraction greenness asymmetry discussed in Section and the competitive-adsorption and defect-characterization gaps noted above, indicate that the translational readiness of MOF-based sorbents, while genuinely promising for several framework–format combinations, remains uneven and should not be overstated on the basis of favorable individual case studies alone.

Overall, the most promising MOF sorbents for routine food analysis are those that combine hydrolytic robustness, low-fouling behavior, scalable synthesis, and verified chemical safety.

4.4. Consolidated Greenness Assessment

The greenness advantages discussed in Section 4.1 and the practical performance evidence in Section 4.2 must ultimately be evaluated against a single, integrated criterion: whether the full analytical workflow from MOF synthesis to analyte determination is more sustainable than the conventional benchmark it replaces. To make this assessment tractable, Table reorganizes seven representative studies from Table against the ten AGREEprep impact categories, using a qualitative three-tier indicator (green, orange, red) derived from the operational parameters reported in each primary publication. This is not intended to substitute formal AGREEprep computation, which requires complete input metadata that is rarely reported in full; rather, it offers a side-by-side visualization of where MOF-based methods systematically perform well, where they are penalized, and where the heterogeneity of the field obscures conclusions. We emphasize that the three-tier color code (aligned/partially aligned/not aligned) used in Table was deliberately chosen instead of a numeric score specifically to avoid conveying a false impression of quantitative precision: unlike AGREEprep, which outputs a single 0–1 score computed from complete, itemized input data, Table conveys only the relative direction of performance per criterion, a convention consistent with established qualitative greenness pictograms such as GAPI, which similarly use color coding without implying a validated numeric score. Readers seeking a fully quantitative, itemized comparison are directed to the primary publications cited in Table , where the underlying operational parameters (sorbent mass, solvent volume, energy input, etc.) are reported in full.

3. Qualitative Assessment Based on Operational Parameters Reported in the Primary Publications; Not a Substitute for Full AGREEprep Computation. Reproduced from Ref 114 with License Number 6344280345630. Copyright 2022 Elsevier.

Two patterns emerge consistently. First, MOF-based microextraction formats (entries 4, 9, 21) score uniformly well on AGREEprep criteria that relate to the extraction step itself: minimal sorbent mass (3–10 mg), low elution volumes (≤500 μL), short extraction times (≤15 min), low waste generation, and good operator safety. This confirms the qualitative narrative of Section 4.1: at the user-facing analytical step, MOF-based sample preparation is genuinely greener than conventional cartridge SPE. Second, however, the same studies score variably and sometimes poorly on AGREEprep criteria that capture upstream aspects, in particular C9 (renewable inputs) and, indirectly, C8 (energy). This reflects the fact that most representative MOFs in food applications are still synthesized solvothermally in DMF or methanol, require activation at 150–250 °C under vacuum for ≥12 h, and frequently incorporate fluorinated linkers (entry 4), heavy or rare metals (Bi in entry 13, Cr in entry 17, Eu in entry 18, Dy in entry 12), or require multistep postsynthetic modification (entries 2, 5, 9). The AGREEprep score of 0.62 reported by Javanmardi et al. is consistent with this pattern: the extraction itself is exemplary, but the synthesis impact suppresses the aggregate score.

This synthesis–extraction greenness asymmetry is the central trade-off that the MOF sample-preparation community must explicitly address. It has two practical consequences. (i) Greenness claims based exclusively on the extraction step are incomplete; a fair comparison against PSA, C18, or GCB should include the cumulative environmental cost of producing one gram of the sorbent, an aspect for which AGREEprep alone is insufficient and which is better captured by complementary metrics such as ComplexGAPI or formal cradle-to-gate life-cycle assessment. (ii) The asymmetry can be partially amortized through sorbent reusability: a MOF synthesized in DMF but reused over ≥30 cycles delivers a substantially lower per-analysis footprint than a single-use conventional sorbent, provided that performance retention is rigorously demonstrated under realistic matrix conditions which, as noted in Section 4.3, is currently the exception rather than the rule.

Mitigation pathways are converging across the recent literature and define the most defensible research agenda for the next 3–5 years: (a) replacement of solvothermal protocols by mechanochemical, microwave-assisted, or aqueous routes, with particular focus on demonstrating equivalence of crystallinity, surface area, and food-matrix performance, not only structural integrity; (b) prioritization of low-toxicity metal nodes (Zr, Al, Fe, Mg, Ca, Ti) and bioderived linkers, with CD-MOFs (entry 21) representing the most advanced food-compatible example; (c) systematic reporting of reusability beyond five cycles, including matrix-aged conditions, so that per-analysis greenness can be calculated rather than assumed; and (d) inclusion of synthesis parameters within published AGREEprep or ComplexGAPI scoring tables, so that future meta-analyses can disaggregate extraction-step from upstream impacts. Only when these four reporting practices become routine will the greenness premise of MOF-based food sample preparation cease to be largely declarative and become quantitatively defensible, a prerequisite for any meaningful translation into SANTE-validated routine practice.

5. Future Outlooks and Conclusions

This review has critically examined the deployment of MOFs and MOF-based composites as sorbents across the full spectrum of food sample preparation formats, and the evidence indicates that MOFs no longer constitute a single emerging material class but rather a structurally and chemically diverse toolbox whose practical readiness varies markedly between framework families and extraction formats. A meaningful future outlook therefore requires distinguishing between what is analytically mature, what is promising but not yet validated in depth, and what remains genuinely speculative. In the first, most mature category, Zr-based frameworks, particularly UiO-66 and UiO-66-NH₂ deployed in MSPE and d-SPE formats, together with their Fe₃O₄-containing magnetic composites, currently represent the most analytically robust MOF-based options for routine food contaminant analysis, supported by multiple independent reports of hydrolytic stability, matrix tolerance, and reusability across pesticides, mycotoxins, and veterinary drug residues. In a second, promising-but-immature category, cyclodextrin-based frameworks (CD-MOFs), fluorinated MOFs (F-MOFs, particularly attractive for PFAS enrichment), lanthanide-based MOFs (Ln-MOFs), MOF-on-MOF composites in D-μ-SPE, and molecularly imprinted MOFs in cartridge SPE show clear conceptual advantages but require systematic benchmarking against established sorbents, broader matrix coverage, and interlaboratory reproducibility data before they can be recommended for routine use. In a third, more speculative category lie directions that are conceptually compelling but currently supported by little food-specific evidence: mechanochemical MOF synthesis as a route to greener material preparation, deep eutectic solvent (DES)-assisted approaches that further reduce the environmental footprint of MOF construction, and AI/ML-guided framework design for the data-driven prediction of stability and adsorption behavior over extensive MOF design spaces; further envisaged developments include food-grade, biocompatible MOFs for contact-relevant applications and the integration of MOF sorbents into automated, online SPE-LC/GC systems and lab-on-a-chip platforms for real-time contaminant monitoring. These three readiness tiers, together with the format-specific maturity assessments provided at the end of Section .8, are consolidated in Table and Figure as an explicit decision matrix, intended to directly answer which MOF-based sorbents and formats are ready for routine food safety laboratories today, and which remain research curiosities requiring further validation.

4. Readiness Assessment of MOF-Based Sorbents for Routine Food Safety Analysis.

readiness tier	MOF family/format	basis for classification
analytically mature	UiO-66/UiO-66-NH2 in MSPE and d-SPE (incl. Fe3O4 magnetic composites)	multiple independent reports of hydrolytic stability, matrix tolerance, >20 reuse cycles, and reusability across pesticides, mycotoxins, veterinary drugs
	MOF-based SPE (cartridge, online, molecularly imprinted)	mature for moderately polar contaminants via online/MIP configurations but constrained by sorbent mass and limited interlab packing-reproducibility data
promising, not yet fully validated	CD-MOFs (food-contact, biocompatible)	conceptually attractive (edible, low-toxicity) but limited matrix coverage and interlaboratory data
	F-MOFs (fluorinated, PFAS-targeted)	strong conceptual fit for PFAS enrichment; requires broader benchmarking against established sorbents
	Ln-MOFs (La–Sm, Dy, Eu)	functional but wide recovery ranges (52.7–135%) across studies; reproducibility not yet established
	MOF-on-MOF composites in D-μ-SPE	attractive greenness profile; evidence base still thin, synthesis complexity and matrix tolerance unverified
	PT-μ-SPE (polymer-supported/substrate-grown MOFs)	practically appealing; tip-to-tip reproducibility and automation compatibility remain under-evaluated
	MOF-based SPME (fiber coatings)	clear promise for PAHs/HPAHs/biogenic amines; fiber-to-fiber reproducibility and coating durability not systematically benchmarked
early stage/speculative	MOF-based SBSE	least developed format; few food applications reported; mechanical durability and bar-to-bar reproducibility require systematic study
	MOF-assisted QuEChERS cleanup	single-laboratory proof-of-concept studies; net greenness gain not yet established against synthesis burden
speculative/research direction	mechanochemical and DES-assisted MOF synthesis	conceptually compelling green-synthesis routes; currently little food-specific performance evidence
	AI/ML-guided MOF design	data-driven prediction of stability/adsorption; not yet demonstrated for food-matrix applications

13.

Readiness assessment of MOF-based sorbents for routine food safety analysis.

Ultimately, the translation of MOFs from laboratory innovation to routine food safety monitoring will depend not only on extraction efficiency but, equally critically, on long-term hydrolytic and mechanical stability under realistic food matrix conditions, batch-to-batch reproducibility, scalable and low-cost synthesis, safety and toxicity assessment for food contact compatibility, and regulatory acceptance within established frameworks such as SANTE. Closing this translational gap, through rigorous validation studies, harmonized reporting of reusability and matrix-dependent performance, and direct benchmarking against PSA, C18, GCB, and polymeric sorbents, is the most likely path by which the analytical promise of MOFs in food sample preparation will become routine practice.

Glossary

Abbreviations

1,4-BDCA

1,4-benzenedicarboxylic acid

AFB1

aflatoxin B1

AGREEprep

analytical greenness metric for sample preparation

AI

artificial intelligence

Al-MOF

aluminum-based metal–organic framework

AMSA

aminomethanesulfonic acid

APTES

3-aminopropyl triethoxysilane

BDC

benzene dicarboxylate (terephthalate)

β-CD

beta-cyclodextrin

BTC

benzene-1,3,5-tricarboxylate

C18

octadecylsilane

C8

octylsilane

CD-MOFs

cyclodextrin metal–organic framework

CE

capillary electrophoresis

CIF

crystallographic information file

CNMMs

cobalt/nickel mixed-metal MOF

CV

coefficient of variation

DABCO

1,4-diazabicyclo [2.2.2] octane

DAD

diode array detector

DES

deep eutectic solvents

d-SPE

dispersive solid-phase extraction

d-μ-SPE

dispersive micro-solid-phase extraction

EF

enrichment factor

EFSA

European Food Safety Authority

FAAS

flame atomic absorption spectrometry

FDA

Food and Drug Administration

FLD

fluorescence detector

GAC

green analytical chemistry

GAPI

Green Analytical Procedure Index

GC–FID

gas chromatography-flame ionization detector

GC–MS

gas chromatography–mass spectrometry

GC–MS/MS

gas chromatography-tandem mass spectrometry

GCB

graphitized carbon black

GO

graphene oxide

GSP

green sample preparation

HAA

heterocyclic aromatic amine

HKUST

Hong Kong University of Science and Technology

HPAHs

halogenated polycyclic aromatic hydrocarbons

HPLC

high-performance liquid chromatography

HSAB

Hard–Soft Acid–Base

ICP–MS

inductively coupled plasma mass spectrometry

IRMOF

isoreticular metal–organic framework

LC–MS

liquid chromatography–mass spectrometry

LC–MS/MS

liquid chromatography-tandem mass spectrometry

LDH

layered double hydroxide

Ln

lanthanides

LOD

limit of detection

LOQ

limit of quantification

MEPS

microextraction by packed sorbents

MIL

Matériaux de l’Institut Lavoisier

ML

machine learning

MIP

molecularly imprinted polymer

MOF

metal–organic framework

MRL

maximum residue limit

MS

mass spectrometry

MSPE

magnetic solid-phase extraction

OPP

organophosphorus pesticide

PAHs

polycyclic aromatic hydrocarbons

PCD

postcolumn derivatization

PDA

polydopamine

PDMS

polydimethylsiloxane

PFAS

per- and polyfluoroalkyl substances

PFCA

perfluoroalkyl carboxylic acid

PFCAs

perfluoroalkyl carboxylic acids

PFOA

perfluorooctanoic acid

PFOS

perfluorooctanesulfonic acid

PSA

primary secondary amine

PSF

polysulfone

PT-μ-SPE

pipette-tip micro-solid-phase extraction

QuEChERS

quick, easy, cheap, effective, rugged, and safe

RSD

relative standard deviation

SBSE

stir bar sorptive extraction

SPE

solid-phase extraction

SPME

solid-phase microextraction

SSW

stainless-steel wire

UHPLC

ultrahigh-performance liquid chromatography

UiO

university of Oslo

UPLC

ultraperformance liquid chromatography

UV

ultraviolet

WHO

World Health Organization

ZIF

zeolitic imidazolate framework

All relevant data are within the paper.

The manuscript was written through contributions of all authors. All authors have given approval of the final version of the manuscript.

The open access publishing of this article is financially supported by HEAL-Link.

The authors declare no competing financial interest.