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. Author manuscript; available in PMC: 2015 Jun 24.
Published in final edited form as: Anal Lett. 2014 Jun 24;47(11):1835–1851. doi: 10.1080/00032719.2014.888727

RECENT ADVANCES IN ULTRA-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY FOR THE ANALYSIS OF TRADITIONAL CHINESE MEDICINE

Huilian Huang 1,2, Min Liu 1, Pei Chen 2,*
PMCID: PMC4100713  NIHMSID: NIHMS602850  PMID: 25045170

Abstract

Traditional Chinese medicine has been widely used for the prevention and treatment of various diseases for thousands of years in China. Ultra-high performance liquid chromatography (UHPLC) is a relatively new technique offering new possibilities. This paper reviews recent developments in UHPLC in the separation and identification, fingerprinting, quantification, and metabolism of traditional Chinese medicine. Recently, the combination of UHPLC with MS has improved the efficiency of the analysis of these materials.

Keywords: UHPLC, Mass Spectrometry, TCM, ultra-high performance liquid chromatography

INTRODUCTION

In 2004, the first commercially available ultra-high performance liquid chromatography (UHPLC) instrument, the Acquity System, became commercially available for separation of small organic molecules, proteins, and peptides (Swartz 2004a, 2004b). UPLC (ultra-high performance liquid chromatography) is a trade name of the Waters Corporation for its system. Using a column packed with 1.7 m particles, UPLC leads to higher separation efficiency for the analysis. At its introduction Waters proclaimed UPLC means “speed, resolution, and sensitivity” (Waters Corporation 2004). UHPLC instruments operate at pressures up to 15,000 psi with faster data collection in comparison to conventional HPLC. Soon after, other liquid chromatography manufacturers developed UHPLC systems. Compared with conventional high-performance liquid chromatography (HPLC), UHPLC gives improved resolution, faster analysis speed, and better sensitivity. It is especially useful for the analysis of traditional Chinese medicine since these materials are complex matrices and the resolution is often insufficient using conventional HPLC. For these reasons, UHPLC currently is widely used for the analysis of traditional Chinese medicines (TCMs).

It is well known that TCMs play an important role in the prevention and treatment of diseases in China (Efferth 2011). TCMs, usually a cocktail of herbal ingredients, have many active constituents and their respective concentrations can be influenced by breeds, origins, growing conditions, and processing techniques. Their effectiveness is commonly considered to involve synergistic effects of all components. Quality control of TCMs is a challenge due to their complexity. UHPLC provides high quality data to identify active compounds in TCM.

UHPLC-Diode Array Detector (UHPLC-DAD) Applications

In comparing two official Chinese pharmacopoeia species of Ganoderma, determination of triterpenes using UHPLC with a diode array detector (DAD) provided identification and quantitation (Da et al. 2012). A method using UHPLC with a DAD detector (UHPLC-DAD) separated about 30 phenolic compounds in Matricaria chamomilla and its crude extracts with a run time about two times faster than a conventional HPLC method (Jing et al. 2013). Moreover, UHPLC requires smaller amounts of solvents than the HPLC approaches (Haghi et al. 2014).

UHPCL-MS Applications

Although there are UHPLC-DAD applications as mentioned in the previous section, UHPLC excels when coupled with mass spectrometry (MS) (Liang et al. 2013; Xu et al. 2012; Wang et al. 2012; Lou et al. 2010). Mass spectrometry is widely used for compound identification and is the most selective detector for compounds from natural products. Mass spectrometers can be classified as HRAM (high resolution accurate mass)-MS and conventional MS, based on resolution and mass accuracy of theirmass analyzers. UHPLC diode array detector (DAD) –MS is very useful for identifying target compounds in TCMs by comparing retention times, ultraviolet absorbance values, molecular ions, and fragmentation data, with or without reference standards. UHPLC coupled with high resolution accurate mass spectrometry (UHPLC-HRAM-MS) reduces analysis time and identifies compounds.

Ninety-two compounds including ginsenosides, lignans, steroidal saponins and homoiso-flavanones were identified by UHPLC-HRAM-MS in Sheng-mai San. This method shows high sensitivity and resolution (Wu et al. 2011). The application of the UHPLC-ESI-MS/MS method allowed the determination of hydroxy fatty acids and phenylethanoids with satisfactory precision (Yang et al. 2013; Gryszczyńska et al. 2012). The HRAM-MS analytical platform has been shown to be fast, sensitive, and reliable for the determination of small molecules in complex matrices (Malik et al. 2010).

UHPLC-Quadrupole Time-of-flight (QTOF) MS

The performance of TOF analyzers has greatly improved in recent years in terms of resolution and mass accuracy (Domon and Aebersold 2006). The combined quadrupole (Q) Q-TOF instrument exhibits high resolution and mass accuracy in MS and MS/MS modes. In MS mode, the quadrupole acts as an ion guide to the TOF analyzer. In MS/MS mode, the precursor ions are selected in the first quadrupole and undergo fragmentation through collision induced dissociation, with product ions analyzed in the TOF device. The combination of UHPLC and Q-TOF technique has accelerated the screening of compounds, while giving excellent separation and good structural characterization abilities which make it suitable to analyze traditional Chinese medicines.

UHPLC-QTOF-MS was used to identify and evaluate a series of components from TCMs, such as coumarin isomers (Lv et al. 2012), phloroglucinol derivatives, diterpenes (Wang et al. 2013), biogenic amines (Jia et al. 2012), quinovic acid glycosides (Pavei et al. 2012), and alkaloids (Jiang et al. 2012). Gahlaut et al. used UHPLC-QTOFMS to distinguish and validate various Saraca asoca extracts and its herbal formulation ‘Ashok arista’ (Gahlaut et al. 2013). Forty components belonging to monoterpene glucosides, galloylglucose, and phenolic compounds of Radix paeoniae were identified by UHPLC-PDA-QTOF-MS (Li et al. 2009).

UHPLC-QTOF-MS/MS has been also applied to separate and characterize steroidal saponins in crude extracts from Dioscorea zingiberensis. A total of thirty-one saponins with five aglycone skeletons, including fourteen new trace saponins, were identified or tentatively elucidated based on their retention times, the mass spectrometric fragmentation patterns, and MS and MS/MS data (Zhu et al. 2010). Similarly, Ji et al. developed a rapid method for xanthones and steroidal saponins of Rhizoma Anemarrhenae (Ji et al. 2012). It was also used for the rapid identification of polymethoxylated flavones in Fructus aurantii (Zhou et al. 2009) and revealed chemical transformation of sulfur-fumigated herbs or the decoction of herbs such as Du–Shen– Tang (Li et al. 2012; Song et al. 2010). In a recent study by Cádiz-Gurrea et al., UHPLCQTOF-MS was used to characterize phenolic compounds in the leaves and flowers of Eryngium bourgatii (Cádiz-Gurrea et al. 2013). It was also used to rapidly screen and identify steroidal saponins from the seeds of Trigonella foenum-graecum and the extract of Paris Polyphylla var. Yunnanensis (Kang et al. 2013a, 2012b).

UHPLC-QTOF was also used for the analysis of Chinese medicine formulae. Eighty-one major constituents such as organic acids, amino acids, oligosaccharides, and alkaloids were separated and identified in Shenqi-Fuzheng injection (Liu et al. 2013). Twenty-two compounds of Suan-zao-ren decoction were tentatively identified using UHPLC-ESI-Q-TOF-MS (Yang et al. 2011). Furthermore, UHPLC-QTOF MS was used to elucidate chemical differences between traditional and dispensing granule decoctions of Tao-Hong-Si-Wu decoction (Shang et al. 2012). In the analysis of aconitum alkaloids in Yin-chen-si-ni decoction, 62 ions were assigned to aconitum alkaloids and identified tentatively by comparing the accurate mass and fragments information with authentic standards or literature reports (Yan et al. 2010). It is also a useful method for finding global chemical differences between traditional and dispensing granule decoctions, and the most changed components during the decoction of San–Huang–Xie–Xin–Tang were identified (Li et al. 2010).

UHPLC-Linear Ion Trap (LTQ)-Orbitrap-MSn

This hybrid configuration provides enhanced selectivity and multiple scan types. Furthermore, no internal calibration is needed to obtain high mass accuracy resulting in a simplified experimental protocol. Based on the HRAM mass information, MS/MS fragmentation behavior, and the literature, forty-three compounds, including new types of saponin aglycones, and malonyl-substituted and acetyl-substituted saponins, were identified in Panax notoginseng (Xu et al. 2012). A total of forty-two diester-diterpenoid alkaloids were separated and identified in the roots of Aconitum carmichaeli by UHPLCLTQ-Orbitrap-MSn. This method has been demonstrated to be an effective tool for the analysis of TCMs (Zhang et al. 2012). Thirty-three compounds, including catechin derivatives, flavanonols, phenolic acid derivatives, and phenylpropanoid glycosides were either identified or tentatively characterized in the rhizome of Smilacis glabrae (Li et al. 2012). The same method was used for the identification of bioactive constituents in Sarcandra glabra and its preparations. Fifty compounds, including organic acids, caffeoyl derivatives, flavonoids, coumarins and terpenoids were identified (Li et al. 2011).

Quantitative Analyses of Targeted Components of TCMs

It is well known that the synergistic actions of TCMs are caused by their multiple constituents. Multi-component quantitative analysis may provide systematic information about TCMs. Many methods using UHPLC with different detection technologies have been used for quantitative analysis of TCMs (Liu et al. 2012; Liang et al. 2010). UHPLC offers reduced analysis time and allows the determination of more compounds compared with conventional HPLC (Kuang et al. 2011). UHPLC-DAD was applied to investigate panaxfurynes A and B from roots of Panax ginseng (Araliaceae) (Lee et al. 2010). Components quantified by this method included flavonoids, rhodiosin, curcuminoids, flavonoid glycosides, and phenylethanoid glycosides (Cao et al. 2012; Zhu et al. 2013; Cheng et al. 2010; Li et al. 2012; Zhao et al. 2013). This method was developed for the determination of narirutin, naringin, hesperidin, neohesperidin, nobiletin, and tangeretin in Fructus aurantii, which provided high chromatographic resolution and rapid analysis (less than 8 min). The samples were also analyzed by UPLC/ESI-Q-TOF-MS to confirm the identification results (Cao et al. 2012).

Rhodiola rosea has been used as an adaptogen in Chinese traditional medicine for centuries. An efficient ionic liquid-based online ultrasonic assisted extraction (UAE) and solid-phase trapping (SPT) method was developed for selective extraction and UPLC quantification of rhodiosin and rhodionin from R. rosea. Cheng et al. developed an UPLC-DAD method, using a C18 (2.1mm × 100mm, 1.7μm) column for rapid quantitation of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in Curcuma longa with an analysis time of 2 min (Cheng et al. 2010). A comprehensive UPLC-DAD method was established to determine the presence of five characteristic phenylethanoid glycosides in the original plants and various commercial products of small-leaved Kudingcha (Ligustrum robustum) and to distinguish this species from similar species, such as the L. henryi, L. lucidum, and L. pricei (Li et al. 2012).

Yang et al. combined nanomagnetic powder three-phase hollow fiber-based liquid-phase microextraction (HF-LPME) with UHPLC-MS for the analysis of nine flavonoids in Polygonum hydropiper, and the results indicate that this method has low detection limits, good reproducibility, and a wide linear range (Yang et al. 2011). A total of twenty-four bioactive components including flavonol glycosides, terpene lactones, biflavones, proanthocyanidins, and ginkgolic acids were quantified in Ginkgo biloba leaves based on a UHPLC-MS/MS method. (Yao et al. 2013). Zearalenone, saponins, and gingerols were determined efficiently using UHPLC-MS (Han et al. 2011; Cheng et al. 2013). Ping Cui et al. applied UHPLC-MS to determine mesaconitine, aconitine, hypaconitine, benzoylmesaconitine, benzoylhypaconitine, and benzoylaconitine (Cui et al. 2012). A method using UHPLC-QTOF-MS was developed for the determination of ginsenosides Rb1, Rb3, Rd, and F2 in Gynostemma pentaphyllum in order to distinguish the sweet and bitter taste variants of a Chinese medicinal tea (Lu et al. 2013).

The determination of many complex components of traditional Chinese preparations like Si-Jun-Zi-Tang, Samhwangsasim-tang, Xue Fu Zhu Yu and Dan-Lou tablets have also been achieved (Zhang et al. 2011; Poudel et al. 2013; Zhang et al. 2012; Dong et al. 2013). Liang et al. combined a UHPLC with a tunable UV detector (UHPLCTUV) and a UHPLC-Q-TOF method for identification and quantification of the main constituents in Niu-Huang-Jie-Du tablets. Ten compounds responsible for the therapeutic effects were determined (Liang et al. 2010). In the analysis for ‘Ge-Gen-Qin-Lian’ tablets and ‘Jiang-Zhi’ granules, UHPLC-MS rapidly determined some components (An et al. 2009; Lu et al. 2010).

Fingerprint Analyses of TCMs by UHPLC

Because TCMs are composed of multiple constituents, quality control based on the quantitative analysis of a few marker compounds does not reflect their overall quality. Consequently, chromatographic fingerprinting is recommended by the Chinese Pharmacopeia (Steinmann et al. 2011; Guan et al. 2011). Fingerprint analysis has also been accepted by the WHO for the assessment of herbal medicines (Jiang et al. 2010). In 2004, “fingerprints” of liquid injections of TCMs were mandated by the Chinese State Food and Drug Administration (SFDA) for quality control (Liang et al. 2004).

UHPLC-MS is a useful approach for rapid pharmaceutical analysis for the differentiation of origin, the determination of authenticity, and the overall quality assessment of herbal medicines. Typical examples for single herb fingerprinting include Physalis alkekengi (Zheng et al. 2012), Radixaconiti (Zhu et al. 2013), Ilex latifolia (Fan et al. 2013), Magnoliae of ficinalis (Wang et al. 2010) and Rhizoma Coptidis chinensis (Kong et al. 2009). Combined with UHPLC and DAD, an established approach to the structural identification of physalins by ESI-MS/MS was applied to the analysis of active extracts of Physalis alkekengi from different locations (Zheng et al. 2012). Zhu et al. established a UHPLC–ESI/MSn fingerprinting approach in combination with chemometric analysis for the quality control of processed Radix aconiti. The results showed that the well processed, unqualified processed, and the raw Radix aconiti clustered corresponding to their constituents by a flexible and reliable method (Zhu et al. 2013).

UHPLC-MS fingerprinting methods are successfully applied for quality assessment of TCMs and to identify major components. Examples include the fingerprint analysis of traditional Chinese formulae like Si-wu decoction (Su et al. 2013), Si-Jun-Zi-Tang (Wang et al. 2013), and Yuan-hu Zhi-tong Tablet (Xu et al. 2013). Eighty-four components were identified or characterized, including ten organic acids, thirty glycosides (monoterpene or iridoid or phenylpropanoids glycosides), fourteen lactones, eighteen flavonoids, and eleven alkaloids in Siwu decoction (Su et al. 2013). A UPLC–QTOF-MS-MS method was used to determine sixty-six major compounds in Si-Jun-Zi-Tang; fifty-eight were tentatively identified. Most major constituents including ginsenosides, licoflavones, and glycyrrhizin in n-butanol extract were studied from Radix ginseng and Glycyrrhiza uralensis (Wang et al. 2013).

Metabolomics by UHPLC in TCMs

Metabolomics, which is the comprehensive assessment of endogenous metabolites of a biological system, is a promising tool for biomarker discovery. The metabolomic approach has done much to further the explore TCMs, and plays an important role for high-throughput elucidation of metabolic phenotypes of crude and processed preparations. Metabolic profiling changes analyzed by UHPLC–MS-MS can be very helpful in understanding TCMs. Chao Ma reported an UHPLC-MS metabolomic approach to characterize the profile of plasma and kidney extract from rats treated with Morning Glory seeds. The results indicate that lysophosphatidylcholine formation and the sphingolipid cycle were accelerated, while the phenylalanine level in serum decreased (Ma et al. 2010). A metabolomic method was developed to establish the profiles of rat plasma to investigate the anti-osteoporosis effect of Rhizoma drynariae and its mechanism. Six potential metabolite biomarkers were identified, including lysophosphatidylcholines, tryptophane, and phenylalanine (Liu et al. 2012). Lu studied the urine metabolite profiling of ‘Kidney-Yang Deficiency syndrome’ induced by hydrocortisone and the positive effect of Rhizoma drynariae in rats by UHPLC-MS (Lu et al. 2011).

There are several UHPLC-Q-TOF/MS reports of metabolomic studies investigating the action mechanism of traditional Chinese medicine. UHPLC-Q-TOF with automated data analysis was applied for rapid analysis of hyperoside metabolites in rat tissue after intravenous administration to understand the mechanism of this compound (Guo et al. 2011). UHPLC–QTOF-MS-based screening has also been used for determining the constituents and their metabolites in rat plasma and urine after oral administration of the Glechoma longituba extract (Ni et al. 2010) and Ping-gan prescription (Jiang et al. 2012). Ultra-performance liquid-chromatography/electrosprayionization synapt high-definition mass spectrometry combined with pattern recognition approaches including principal component analysis (PCA) were integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites. These practices are promising for profiling TCMs and using the metabolomic platform (Yang et al. 2012). UHPLC-HRAM-MS combined with a principal component analysis (PCA) was used for exploring the excretion pattern of low molecular mass metabolites (Wang et al. 2010), to study the metabolomic characteristics and the micromolecular marking compound of urine, and to study the efficacy and mechanism of complex TCM prescriptions with a rapid and noninvasive urinary metabolomics approach (Su et al. 2011; Sun et al. 2010).

Aconite root, an herbal medicine in TCM, has a very narrow therapeutic range. An approach based on UHPLC-HRAM-MS with a metabolomic approach was employed to demonstrate the plasma characteristics, speculate on alternative pathways, and compare differences between the crude and processed products. The study provides information to further understand the pharmacological activity and potential toxicity of processed Aconite roots (Wang et al. 2012). Pyrrolizidine alkaloids show significant hepatotoxicity as they bind to DNA or proteins after activation in the liver. A metabolomic study using UHPLC-MS to obtain the profiles of Senecio scandens and S. vulgaris was reported. This study provided a better understanding of the toxicities of two Senecio herbs containing pyrrolizidine alkaloids (Xiong et al. 2011)

Pharmacokinetic Applications by UHPLC in TCMs

The traditional approach of determining metabolites from biological samples involves isolation by column chromatography or preparative HPLC unless reference standards are available. It is a very expensive, laborious, and time-consuming process. UHPLC-HRAM-MS can provide information on the structure of the metabolites much faster, especially when a database is available. Numerous reports have shown the use of UHPLC to explore the efficacy and mechanism of TCMs.

UHPLC-MS pharmacokinetic studies of TCMs have been performed by many groups (Yang et al. 2012; Li et al. 2012; Qiu et al. 2011;Yin et al. 2012; Gan et al. 2012; Xiong et al. 2010; Wang, et al. 2011; Sun et al. 2012). A pharmaco-metabolomics study to explore the therapeutic basis and to clarify the mechanism of traditional Chinese medicine by UHPLC-MS has also been reported (Sun et al. 2013; Zhang et al. 2011).

Pharmacokinetic studies on active constituents in TCMs are used to explain and predict the efficacy and toxicity. A rapid, sensitive and selective UHPLC–MS-MS method was developed for determination of the bioactive components and their metabolites in rat plasma after the administration of Shaofu Zhuyu decoction. Nine metabolites were identified in rat plasma based on the mass fragmentation and literature reports (Su et al. 2010). Guo et al. investigated the anticonvulsant and antidepressant-like effects of Abelmoschus manihot ethanol extract as well as its potential active components in vivo. Eight flavonoids were identified in rat brain after its administration by UHPLCMS (Guo et al. 2011).

UHPLC–Q-TOF-MS was used to determine constituents in rat biological fluids after oral administration of Fufang Danshen tablets. In vivo, fourteen components and eight metabolites of FDT were observed in plasma, and twelve components were detected in urine (Lv et al. 2010). Zhong et al. used UHPLC-Q–TOF–MS to determine the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi capsules (Zhong et al. 2012). Another UHPLC–HRMS method was developed to analyze and identify the bioactive components and their metabolites in rat plasma following oral administration of Radix stemonae extract. The method could be applied to other TCMs (Dong et al. 2012). The structure and metabolite profile of eleutheroside B were elucidated by a UHPLC-Q-TOF MS method (Lu et al. 2012).

UHPLC-MS is a selective and sensitive method that can also be used effectively to quantify bioactive components in vivo. Many quantitative methods, including validated methods, were successfully applied to investigate the pharmacokinetics of the bioactive compounds in rats. Puerarin, daidzein, baicalin, wogonoside, and liquiritin of Ge-gen-Qin-lian decoction were determined in rat plasma using UHPLC–MS (Wang et al. 2009). A UHPLC-MS/MS method for koumine determination in rat plasma after a single intravenous dose of 20 mg/kg was validated (Chen et al. 2013). The quantification of ephedrine in Herba ephedrae and Wu-Tou-Tang decoctions in rat plasma were also studied using UHPLC-MS (Zheng et al. 2012). Quantitation of ligustilide, dehydrocostuslactone, α-cyperone (Liu et al. 2013), psoralen, isopsoralen (Gu et al. 2009), pimpinellin, isopimpinellin, phellopterin (Liu et al. 2012), paeoniflorin, naringin, naringenin, glycyrrhetinic (Wen et al. 2012), and three physalins (Zheng et al. 2012) in rats by UHPLC-MS/MS have also been reported.

Tao et al. developed a UHPLC-MS-MS method which was successfully applied to a pharmacokinetic study of eight triterpenoid saponins including uralsaponin C, uralsaponin F, 22β-acetoxyl-glycyrrhizin, 24-hydroxy-licorice-saponin E2, licorice-saponin G2, licorice-saponin E2, glycyrrhizin, and licorice-saponin J2 in dog plasma after oral administration of total saponin of licorice (Tao et al. 2013). Wang et al. used an UHPLC-TOF-MS method to determine fifteen ginsenosides and metabolites and their bioavailability in humans. Compared to conventional HPLC method, the UHPLC method has significant advantages in high-speed separation and rapid resolution. Ginsenosides Rb1, Rd, Rg2, and compound K were detected in the plasma samples and enteric microbiota are responsible for metabolism of parent ginsenosides to compound K (C.Z. Wang et al. 2011).

Microdialysis allows the determination of drug concentrations in blood and tissues. This technique may be applied to pharmacokinetic studies without depriving the subject of biological fluids and disturbing physiological functions. Microdialysis was combined with UHPLC-MS to determine ligustilide in rat brains. This method uses fewer animals and demonstrated use with UHPLC-MS for pharmacokinetic studies (Guo et al. 2011). Xue et al. combined microdialysis with UHPLC–Q-TOF-MS to identify components in blood and kidney dialysis after oral administration of Abelmoschus manihot extract. This method was simple and reliable, and could be adopted to rapidly screen and identify potential active components contributing to pharmacological effects of TCMs (C.F. Xue et al. 2011).

Preliminary screening, systematic screening and processing technology investigation also can be accomplished by UHPLC. For instance, Kong et al. proposed a novel “target constituent knock-out” strategy coupled for preliminary screening of antibacterial constituents in Calculus bovis (Kong et al. 2011). Moreover, systematic screening of tertiary and quaternary alkaloids from Corydalis yanhusuo and processing technology investigation of Loquat leaf (Eriobotrya japonica ) were performed based on UHPLC-QTOF-MS (Zhang et al. 2009; Wu et al. 2013).

CONCLUSIONS

Traditional Chinese medicines have been used for centuries for the prevention and treatment of human disease. Over the past decades, traditional herbal medicines have been an important resource for screening lead compounds. HPLC is a predominant technology used in laboratories worldwide, and made a significant contribution to the modernization of Chinese traditional medicines during the past 40 years. UHPLC is a relatively new technique providing decreased analysis time and solvent consumption. UHPLC retains the practicality and principles of HPLC while providing improvement in performance. It is evident that the use of UHPLC is advantageous in terms of speed for analyses requiring up to 80,000 theoretical plates. This opens the options for reducing the analysis time of current HPLC procedures (Villiers et al. 2006). UHPLC coupled with MS provides accurate mass measurement, high resolution, and selectivity, and is an important tool for the determination of constituents in TCMs.

ACKNOWLEDGEMENTS

This research is supported by the Agricultural Research Service of the U.S. Department of Agriculture and an Interagency Agreement with the Office of Dietary Supplements of the National Institutes of Health, the National Natural Science Foundation of China (NSFC) (No.31370376 and No.81160507), and the Project of University's Young Teachers’ Development of Jiangxi Province, China (2012-132).

REFERENCES

  1. An R, Wang Y, You LS, Wang XH. UPLC–MS Analysis for Simultaneous Determination of Eight Components in the ‘Ge-Gen-Qin-Lian’ Tablets. Chromatographia. 2009;69:969–975. [Google Scholar]
  2. Cádiz-Gurrea MDLL, Fernández-Arroyo S, Joven J, Segura-Carretero A. Comprehensive characterization by UPLC-ESI-Q-TOF-MS from an Eryngium bourgatii extract and their antioxidant and anti-inflammatory activities. Food Res. Int. 2013;50:197–204. [Google Scholar]
  3. Cao JL, Zhou SJ, Qiu F, Kong WJ, Wan L, Yang MH. A simple and fast method for the simultaneous quantification of six flavonoids in Fructus aurantii by UPLC–PDA and confirmation by UPLC/ESI-Q-TOF-MS. Anal. Methods-UK. 2012;4:4121–4128. [Google Scholar]
  4. Chen JZ, Li Y, Xiao JP, Wu SS, Song HW. Development of a sensitive and rapid UPLC-MS /MS method for the determination of koumine in rat plasma: application to a pharmacokinetic study. Biomed.Chromatogr. 2013;27:736–740. doi: 10.1002/bmc.2852. [DOI] [PubMed] [Google Scholar]
  5. Cheng J, Kong WJ, Luo Y, Wang JB, Wang HT, Li QM, Xiao XH. Development and validation of UPLC method for quality control of Curcuma longa Linn.: Fast simultaneous quantitation of three curcuminoids. J. Pharm. Biomed. Anal. 2010;53:43–49. doi: 10.1016/j.jpba.2010.03.021. [DOI] [PubMed] [Google Scholar]
  6. Cheng XL, Qi LW, Wang Q, Liu XG, Boubertakh B, Wan JY, Liu EH, Li P. Highly efficient sample preparation and quantification of constituents from traditional Chinese herbal medicines using matrix solid-phase dispersion extraction and UPLC-MS/MS. Analyst. 2013;138:2279–2288. doi: 10.1039/c3an36732k. [DOI] [PubMed] [Google Scholar]
  7. Cui P, Han H, Wang R, Yang L. Identification and determination of Aconitum alkaloids in Aconitum herbs and Xiaohuoluo pill using UPLC-ESI-MS. Molecules. 2012;17:10242–10257. doi: 10.3390/molecules170910242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Da J, Wu WY, Hou JJ, Long HL, Yao S, Yang Z, Cai LY, Yang M, Jiang BH, Liu X, Cheng CR, Li YF, Guo DA. Comparison of two officinal Chinese pharmacopoeia species of Ganoderma based on chemical research with multiple technologies and chemometrics analysis. J. Chromatogr. A. 2012;1222:59–70. doi: 10.1016/j.chroma.2011.12.017. [DOI] [PubMed] [Google Scholar]
  9. Domon B, Aebersold R. Mass spectrometry and protein analysis. Science. 2006;312:212–217. doi: 10.1126/science.1124619. [DOI] [PubMed] [Google Scholar]
  10. Dong J, Zhu Y, Gao XM, Chang YX, Wang M, Zhang P. Qualitative and quantitative analysis of the major constituents in Chinese medicinal preparation Dan-Lou tablet by ultra high performance liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry. J. Pharm. Biomed. Anal. 2013;80:50–62. doi: 10.1016/j.jpba.2013.02.011. [DOI] [PubMed] [Google Scholar]
  11. Dong W, Wang P, Meng XC, Sun H, Zhang AH, Wang WM, Dong H, Wang XJ. Ultra-performance Liquid Chromatography–High-definition Mass Spectrometry Analysis of Constituents in the Root of Radix Stemonae and those Absorbed in Blood after Oral Administration of the Extract of the Crude Drug. Phytochem. Anal. 2012;23:657–667. doi: 10.1002/pca.2370. [DOI] [PubMed] [Google Scholar]
  12. Efferth T. Perspectives for Globalized Natural Medicines. Chin. J. Nat. Med. 2011;9:1–6. [Google Scholar]
  13. Fan CL, Deng JW, Yang YY, Liu JS, Wang Y, Zhang XQ, Fai KC, Zhang QW, Ye WC. Multi-ingredients determination and fingerprint analysis of leaves from Ilex latifolia using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J. Pharm. Biomed. Anal. 2013;84:20–29. doi: 10.1016/j.jpba.2013.05.039. [DOI] [PubMed] [Google Scholar]
  14. Gahlaut A, Shirolkar A, Hooda V, Dabur R. A rapid and simple approach to discriminate various extracts of Saraca asoca [Roxb.], De. Wild using UPLC-QTOFMS and multivariate analysis. J. Pharm. Res. 2013;7:143–149. [Google Scholar]
  15. Gan PP, Zhong MZ, Huang X, Sun M, Wang Y, Xiao YY, Zeng C, Yuan QJ, Liu ZQ, Zhou HH. Pharmacokinetic Comparisons of Albiflorin and Paeoniflorin after Oral Administration of Shaoyao-Gancao-Tang and Single Herb Paeony Decoction to Rats. Planta Med. 2012;78:237–243. doi: 10.1055/s-0031-1280366. [DOI] [PubMed] [Google Scholar]
  16. Gryszczyńska A, Łowicki Z, Opala B, Krajewska-Patan A, BuchWald W, Czerny B, Mielcarek S, Mrozikiewicz PM. Comparison of phenylethanoids content in Rhodiola kirilowii and Rhodiola rosea roots applying a newly developed UPLC-MS/MS method. Herba Pol. 2012;58:29–39. [Google Scholar]
  17. Gu Y, Si DY, Gao J, Zeng Y, Liu CX. Liu.Simultaneous quantification of psoralen and isopsoralen in rat plasma by ultra-performance liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study after oral administration of Haigou Pill. J. Chromatogr. B. 2009;877:3137–3143. doi: 10.1016/j.jchromb.2009.07.035. [DOI] [PubMed] [Google Scholar]
  18. Guan TY, Liang Y, Li CZ, Xie L, Wang GJ, Sheng LS. Recent development in liquid chromatography/mass spectrometry and allied topics for traditional Chinese medicine research. Chin. J. Nat. Med. 2011;9:385–400. [Google Scholar]
  19. Guo J, Xue C, Duan JA, Qian D, Tang Y, You Y. Anticonvulsant, antidepressant-like activity of Abelmoschus manihot ethanol extract and its potential active components in vivo. Phytomedicine. 2011;18:1250–1254. doi: 10.1016/j.phymed.2011.06.012. [DOI] [PubMed] [Google Scholar]
  20. Guo JM, Xue CF, Shang EX, Duan JA, Tang YP, Qian DW. Identification of hyperoside metabolites in rat using ultra performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry. J. Chromatogr. B. 2011;879:1987–1992. doi: 10.1016/j.jchromb.2011.04.031. [DOI] [PubMed] [Google Scholar]
  21. Guo JM, Shang EX, Duan JA, Tang YP, Qian DW. Determination of ligustilide in the brains of freely moving rats using microdialysis coupled with ultra performance liquid chromatography/mass spectrometry. Fitoterapia. 2011;82:441–445. doi: 10.1016/j.fitote.2010.12.002. [DOI] [PubMed] [Google Scholar]
  22. Haghi G, Hatami A, Safaeiand A, Mehran M. Analysis of phenolic compounds in Matricaria chamomilla and its extracts by UPLC-UV. Res. Pharm. Sci. 2014;9:31–37. [PMC free article] [PubMed] [Google Scholar]
  23. Han Z, Ren YP, Zhou HL, Luan LJ, Cai ZX, Wu YJ. A rapid method for simultaneous determination of zearalenone, alpha-zearalenol, beta-zearalenol, zearalanone, alpha-zearalanol and beta-zearalanol in traditional Chinese medicines by ultra-high-performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. B. 2011;879:411–420. doi: 10.1016/j.jchromb.2010.12.028. [DOI] [PubMed] [Google Scholar]
  24. Ji X, Feng YF, Rui W. Rapid Analysis of Xanthones and Steroidal Saponins in Extract of Rhizoma Anemarrhenae by Ultra-performance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry. 2012 International Conference on Biomedical Engineering and Biotechnology. 2012:477–485. [Google Scholar]
  25. Jia SD, Kang YP, Park JH, Lee J, Kwon SW. Determination of biogenic amines in Bokbunja (Rubus coreanus Miq.) wines using a novel ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry. Food Chem. 2012;132:1185–1190. doi: 10.1016/j.foodchem.2011.11.069. [DOI] [PubMed] [Google Scholar]
  26. Jiang HQ, Nie L, Li YL, Xie J. Application of ultra-performance liquid chromatography coupled with mass spectrometry to metabonomic study on spontaneously hypertensive rats and intervention effects of Ping Gan prescription. J. Sep. Sci. 2012;35:483–489. doi: 10.1002/jssc.201100769. [DOI] [PubMed] [Google Scholar]
  27. Jiang X, Huang LF, Wu LB, Wang ZH, Chen SL. UPLC-QTOF/MS Analysis of Alkaloids in Traditional Processed Coptis chinensis Franch. Evid-based Compl. Alt. 2012;2012:1–6. doi: 10.1155/2012/942384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jiang Y, David B, Tu PF, Barbin Y. Recent analytical approaches in quality control of traditional Chinese medicines--a review. Analytica chimica acta. 2010;657:9–18. doi: 10.1016/j.aca.2009.10.024. [DOI] [PubMed] [Google Scholar]
  29. Jing J, Parekh HS, Wei M, Ren WC, Chen SB. Advances in analytical technologies to evaluate the quality of traditional Chinese medicines. TrAC, Trends Anal. Chem. 2013;44:39–45. [Google Scholar]
  30. Kang LP, Yu K, Zhao Y, Liu YX, Yu HS, Pang X, Xiong CQ, Tan DW, Gao Y, Liu C, Ma BP. Characterization of steroidal glycosides from the extract of Paris Polyphylla var.Yunnanensis by UPLC/Q-TOF MSE. J. Pharm. Biomed. Anal. 2012;62:235–249. doi: 10.1016/j.jpba.2011.12.027. [DOI] [PubMed] [Google Scholar]
  31. Kang LP, Zhao Y, Pang X, Yu HS, Xiong CQ, Zhang J, Gao Y, Yu K, Liu C, Ma BP. Characterization and identification of steroidal saponins from the seeds of Trigonella foenum-graecum by ultra high-performance liquid chromatography and hybrid time-of-flight mass spectrometry. J. Pharm. Biomed. Anal. 2013;74:257–267. doi: 10.1016/j.jpba.2012.11.005. [DOI] [PubMed] [Google Scholar]
  32. Kong WJ, Wang JB, Zang QC, Jin C, Wang ZW, Xing XY, Wu YY, Zhao YL, Yang MH, Xiao XH. A novel “target constituent knock-out” strategy coupled with TLC, UPLC-ELSD and microcalorimetry for preliminary screening of antibacterial constituents in Calculus bovis. J. Chromatogr. B. 2011;879:3565–3573. doi: 10.1016/j.jchromb.2011.09.045. [DOI] [PubMed] [Google Scholar]
  33. Kong WJ, Zhao YL, Xiao XH, Jin C, Li ZL. Quantitative and chemical fingerprint analysis for quality control of rhizoma Coptidischinensis based on UPLC-PAD combined with chemometrics methods. Phytomedicine. 2009;16:950–959. doi: 10.1016/j.phymed.2009.03.016. [DOI] [PubMed] [Google Scholar]
  34. Kuang HX, Xia YG, Liang J, Yang BY, Wang QH, Sun YP. Fast classification and compositional analysis of polysaccharides from TCMs by ultra-performance liquid chromatography coupled with multivariate analysis. Carbohydr. Polym. 2011;84:1258–1266. [Google Scholar]
  35. Lee SM, Lee HB, Lee CG. A convenience UPLC/PDA method for the quantitative analysis of panaxfuraynes A and B from Panax ginseng. Food Chem. 2010;123:955–958. [Google Scholar]
  36. Li GW, Zeng XL, Xie Y, Cai ZZ, Moore JC, Yuan XR, Cheng ZH, Ji G. Pharmacokinetic properties of isorhamnetin, kaempferol and quercetin after oral gavage of total flavones of Hippophae rhamnoides L. in rats using a UPLC–MS method. Fitoterapia. 2012;83:182–191. doi: 10.1016/j.fitote.2011.10.012. [DOI] [PubMed] [Google Scholar]
  37. Li L, Xu LJ, Peng Y, He ZD, Shi RB, Xiao PG. Simultaneous determination of five phenylethanoid glycosides in small-leaved Kudingcha from the Ligustrum genus by UPLC/PDA. Food Chem. 2012;131:1583–1588. [Google Scholar]
  38. Li SL, Shen H, Zhu LY, Xu J, Jia XB, Zhang HM, Lin G, Cai H, Cai BC, Chen SL, Xu HX. Ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry based chemical profiling approach to rapidly reveal chemical transformation of sulfur-fumigated medicinal herbs, a case study on white ginseng. J. Chromatogr. A. 2012;1231:31–45. doi: 10.1016/j.chroma.2012.01.083. [DOI] [PubMed] [Google Scholar]
  39. Li SL, Lai SF, Song JZ, Qiao CF, Liu X, Zhou Y, Cai H, Cai BC, Xu HX. Decocting-induced chemical transformations and global quality of Du–Shen–Tang, the decoction of ginseng evaluated by UPLC–Q-TOF-MS/MS based chemical profiling approach. J. Pharm. Biomed. Anal. 2010;53:946–957. doi: 10.1016/j.jpba.2010.07.001. [DOI] [PubMed] [Google Scholar]
  40. Li SL, Song JZ, Choi FFK, Qiao CF, Zhou Y, Han QB, Xu HX. Chemical profiling of Radix Paeoniae evaluated by ultra-performance liquid chromatography/photo-diode-array/Quadrupole time-of-flight mass spectrometry. J. Pharm. Biomed. Anal. 2009;49:253–266. doi: 10.1016/j.jpba.2008.11.007. [DOI] [PubMed] [Google Scholar]
  41. Li SL, Song JZ, Qiao CF, Zhou Y, Xu HX. UPLC-PDA-TOFMS based chemical profiling approach to rapidly evaluate chemical consistency between traditional and dispensing granule decoctions of traditional medicine combinatorial formulae. J. Pharm. Biomed. Anal. 2010;52:468–478. doi: 10.1016/j.jpba.2010.01.032. [DOI] [PubMed] [Google Scholar]
  42. Li XH, Xiong ZL, Lu S, Zhang Y, Li FM. Pharmacokinetics of Naringin and its Metabolite Naringenin in Rats after Oral Administration of Rhizoma Drynariae Extract Assayed by UPLC-MS/MS. Chin. J. Nat. Med. 2010;8:40–46. [Google Scholar]
  43. Li X, Zhang YF, Yang L, Feng Y, Deng YH, Liu YM, Zeng X. Chemical profiling of constituents of Smilacis glabrae using ultra-high pressure liquid chromatography coupled with LTQ Orbitrap mass spectrometry. Nat Prod Commun. 2012;7(2):181–184. [PubMed] [Google Scholar]
  44. Li X, Zhang YF, Zeng X, Yang L, Deng YH. Chemical profiling of bioactive constituents in Sarcandra glabra and its preparations using ultra-high-pressure liquid chromatography coupled with LTQ Orbitrap mass spectrometry. Rapid Commun. Mass Spectrom. 2011;25:2439–2447. doi: 10.1002/rcm.5123. [DOI] [PubMed] [Google Scholar]
  45. Liang Q, Ma J, Ma ZC, Wang YG, Tan HL, Xiao CR, Liu M, Lu BB, Zhang BL, Gao Y. Chemical comparison of dried rehmannia root and prepared rehmannia root by UPLC-TOF MS and HPLC-ELSD with multivariate statistical analysis. Acta Pharm. Sinic. B. 2013;3:55–64. [Google Scholar]
  46. Liang YZ, Xie PS, Chan K. Quality control of herbal medicines. J. Chromatogr. B. 2004;812:53–70. doi: 10.1016/j.jchromb.2004.08.041. [DOI] [PubMed] [Google Scholar]
  47. Liu MH, Tong X, Wang JX, Zou W, Cao H, Su WW. Rapid separation and identification of multiple constituents in traditional Chinese medicine formula Shenqi Fuzheng Injection by ultra-fast liquid chromatography combined with quadrupole-time-of-flight mass spectrometry. J. Pharm. Biomed. Anal. 2013;74:141–155. doi: 10.1016/j.jpba.2012.10.024. [DOI] [PubMed] [Google Scholar]
  48. Liu P, Li ZH, Qian DW, Li W, Shang EX, Duan JA. Simultaneous determination of bioactive components in essential oil of Xiang–Fu–Si–Wu Formula in Beagle dog plasma by UPLC–MS/MS and its application to pharmacokinetics. J. Chromatogr. B. 2013;929:63–69. doi: 10.1016/j.jchromb.2013.04.022. [DOI] [PubMed] [Google Scholar]
  49. Liu XH, Xu CH, Sun SQ, Huang J, Zhang K, Li GY, Zhu Y, Zhou Q, Zhang ZC, Wang JH. Discrimination of different genuine Danshen and their extracts by Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy. Spectrochim. Acta A Mol. Biomo Spectrosc. 2012;97:290–296. doi: 10.1016/j.saa.2012.06.013. [DOI] [PubMed] [Google Scholar]
  50. Liu XY, Zhang SS, Lu XM, Zheng SN, Li FM, Xiong ZL. Metabonomic study on the anti-osteoporosis effect of Rhizoma Drynariae and its action mechanism using ultra-performance liquid chromatography–tandem mass spectrometry. J. Ethnopharmacol. 2012;139:311–317. doi: 10.1016/j.jep.2011.11.017. [DOI] [PubMed] [Google Scholar]
  51. Liu ZG, Jiang MY, Lu XM, Qin F, Song Y, Wen J, Li FM. Simultaneous determination of pimpinellin, isopimpinellin and phellopterin in rat plasma by a validated UPLC–MS/MS and its application to a pharmacokinetic study after administration of Toddalia asiatica extract. J. Chromatogr. B. 2012;891-892:102–108. doi: 10.1016/j.jchromb.2012.02.022. [DOI] [PubMed] [Google Scholar]
  52. Lou ZX, Wang HX, Zhu S, Zhang M, Gao Y, Ma CY, Wang ZP. Improved extraction and identification by ultra performance liquid chromatography tandem mass spectrometry of phenolic compounds in burdock leaves. J. Chromatogr. A. 2010;1217:2441–2446. doi: 10.1016/j.chroma.2009.12.022. [DOI] [PubMed] [Google Scholar]
  53. Lu F, Sun Q, Bai Y, Bao SR, Li XZ, Yan GL, Liu SM. Characterization of eleutheroside B metabolites derived from an extract of Acanthopanax senticosus Harms by high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Biomed. Chromatogr. 2012;26:1269–1275. doi: 10.1002/bmc.2688. [DOI] [PubMed] [Google Scholar]
  54. Lu JG, Zhu L, Lo KYW, Leung AKM, Ho AHM, Zhang HY, Zhao ZZ, Fong DWF, Jiang ZH. Chemical differentiation of two taste variants of Gynostemma pentaphyllum by using UPLC-Q-TOF-MS and HPLC-ELSD. J. Agric. Food. Chem. 2013;61:90–97. doi: 10.1021/jf304154d. [DOI] [PubMed] [Google Scholar]
  55. Lu XM, Xiong ZL, Li JJ, Zheng SN, Huo TG, Li FM. Metabonomic study on ‘Kidney-Yang Deficiency syndrome’ and intervention effects of Rhizoma Drynariae extracts in rats using ultra performance liquid chromatography coupled with mass spectrometry. Talanta. 2011;83:700–708. doi: 10.1016/j.talanta.2010.09.026. [DOI] [PubMed] [Google Scholar]
  56. Lu YL, Wang M, Zhang L, He YQ, Yang L, Wang CH, Wang ZT, Ji G. Simultaneous Determination of Six Components in the ‘Jiang-Zhi’ Granule by UPLC-MS Analysis. Chin. J. Nat. Med. 2010;8:449–455. [Google Scholar]
  57. Lv HW, Luo JG, Wang XB, Kong LY. Application of UPLC-Quadrupole-TOF-MS Coupled with Recycling Preparative HPLC in Isolation and Preparation of Coumarin Isomers with Similar Polarity from Peucedanum praeruptorum. Chromatographia. 2013;76:141–148. [Google Scholar]
  58. Lv YH, Zhang X, Liang X, Liu XR, Dai WX, Yan SK, Zhang WD. Characterization of the constituents in rat biological fluids after oral administration of Fufang Danshen tablets by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J. Pharm. Biomed. Anal. 2010;52:155–159. doi: 10.1016/j.jpba.2009.12.013. [DOI] [PubMed] [Google Scholar]
  59. Ma C, Bi KS, Su D, Ji W, Zhang M, Fan XX, Wang C, Chen XH. Serum and kidney metabolic changes of rat nephrotoxicity induced by Morning Glory Seed. Food Chem. Toxicol. 2010;48:2988–2993. doi: 10.1016/j.fct.2010.07.038. [DOI] [PubMed] [Google Scholar]
  60. Malik AK, Blasco C, Picó Y. Liquid chromatography-mass spectrometry in food safety. J. Chromatogr. A. 2010;1217:4018–4040. doi: 10.1016/j.chroma.2010.03.015. [DOI] [PubMed] [Google Scholar]
  61. Ni SM, Qian DW, Duan JA, Guo JM, Shang EX, Shu Y, Xue CF. UPLC–QTOF/MS-based screening and identification of the constituents and their metabolites in rat plasma and urine after oral administration of Glechoma longituba extract. J. Chromatogr. B. 2010;878:2741–2750. doi: 10.1016/j.jchromb.2010.08.014. [DOI] [PubMed] [Google Scholar]
  62. Pavei C, Kaiser S, Verza SG, Borre GL, Ortega GG. HPLC-PDA method for quinovic acid glycosides assay in Cat's claw (Uncaria tomentosa) associated with UPLC/Q-TOF-MS analysis. J. Pharm. Biomed. Anal. 2012;62:250–257. doi: 10.1016/j.jpba.2011.12.031. [DOI] [PubMed] [Google Scholar]
  63. Poudel A, Kim SG, Lamichhane R, Kim YK, Jo HK, Jung HJ. Quantitative Assessment of Traditional Oriental Herbal Formulation Samhwangsasim-tang Using UPLC Technique. J. Chromatogr. Sci. 2013:1–10. doi: 10.1093/chromsci/bmt008. [DOI] [PubMed] [Google Scholar]
  64. Qiu XJ, Huang X, Chen ZQ, Ren P, Huang W, Qin F, Hu SH, Huang J, He J, Liu ZQ, Zhou HH. Pharmacokinetic study of the prokinetic compounds meranzin hydrate and ferulic acid following oral administration of Chaihu-Shugan-San to patients with functional dyspepsia. J. Ethnopharmacol. 2011;137:205–213. doi: 10.1016/j.jep.2011.05.009. [DOI] [PubMed] [Google Scholar]
  65. Shang EX, Zhu ZH, Liu L, Tang YP, Duan JA. UPLC-QTOF-MS with chemical profiling approach for rapidly evaluating chemical consistency between traditional and dispensing granule decoctions of Tao-Hong-Si-Wu decoction. Chem. Cent. J. 2012;6:143. doi: 10.1186/1752-153X-6-143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Shi J, Wang YM, Luo GA. UPLC-TOF MS-Based Metabonomic Study on Coadministration of Huperzine A and Ligustrazine Phosphate for Treatment of Alzheimer's Disease. Chromatographia. 2011;74:827–832. [Google Scholar]
  67. Steinmann D, Ganzera M. Recent advances on HPLC/MS in medicinal plant analysis. J. Pharm. Biomed. Anal. 2011;55:744–757. doi: 10.1016/j.jpba.2010.11.015. [DOI] [PubMed] [Google Scholar]
  68. Swartz ME. Presentation at the Pitts, Conf. on Anal. Chem. Appl. Spectrosc. Chicago, IL: 2004. [Google Scholar]
  69. Su SL, Cui WX, Zhou W, Duan JA, Shang EX, Tang YP. Chemical fingerprinting and quantitative constituent analysis of Siwu decoction categorized formulae by UPLC-QTOF/MS/MS and HPLC-DAD. Chinese Med. 2013;8:5. doi: 10.1186/1749-8546-8-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Su SL, Guo JM, Duan JA, Wang TJ, Qian DW, Shang EX, Tang YP. Ultra-performance liquid chromatography–tandem mass spectrometry analysis of the bioactive components and their metabolites of Shaofu Zhuyu decoction active extract in rat plasma. J. Chromatogr. B. 2010;878:355–362. doi: 10.1016/j.jchromb.2009.11.048. [DOI] [PubMed] [Google Scholar]
  71. Su ZH, Li SQ, Zou GA, Yu CY, Sun YG, Zhang HW, Gu Y, Zou ZM. Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats. J. Pharm. Biomed. Anal. 2011;55:533–539. doi: 10.1016/j.jpba.2011.02.013. [DOI] [PubMed] [Google Scholar]
  72. Sun H, Wu FF, Zhang AH, Wei WF, Han Y, Wang XJ. Pharmacokinetic study of schisandrin, schisandrol B, schisantherin A , deoxyschisandrin, and schisandrin B in rat plasma afterorala dministration of Shengmaisan formula by UPLC-MS. J. Sep. Sci. 2013;36:485–491. doi: 10.1002/jssc.201200887. [DOI] [PubMed] [Google Scholar]
  73. Sun H, Yin QW, Zhang AH, Wang XJ. UPLC–MS/MS performing pharmacokinetic and biodistribution studies of rhein. J. Sep. Sci. 2012;35:2063–2068. doi: 10.1002/jssc.201200378. [DOI] [PubMed] [Google Scholar]
  74. Sun P, Luo GA, Qiao MQ, Wei S, Huang H, Wei N, Zhang HY, Song HY. Studies on the Metabonomics of Premenstrual Syndrome Liver-Qi Invasion Patient Interfered by Jingqianping Granules. Mode Tradit. Chin. Med. Mater. Med. 2010;12:195–201. [Google Scholar]
  75. Tao WW, Duan JN, Guo JM, Li JP, Tang YP, Liu P, Yang NY. Simultaneous determination of triterpenoid saponins in dog plasma by a validated UPLC–MS/MS and its application to a pharmacokinetic study after administration of total saponin of licorice. J. Pharm. Biomed. Anal. 2013;75:248–255. doi: 10.1016/j.jpba.2012.11.035. [DOI] [PubMed] [Google Scholar]
  76. Villiers AD, Lestremau F, Szucs R, Gélébart S, David F, Sandra P. Evaluation of ultra performance liquid chromatography Part I. Possibilities and limitations. J. Chromato. A. 2006;1127:60–69. doi: 10.1016/j.chroma.2006.05.071. [DOI] [PubMed] [Google Scholar]
  77. Wang CJ, Jiang YQ, Liu DH, Yan XH, Ma SC. Characterization of phloroglucinol derivatives and diterpenes in Euphorbia ebracteolata Hayata by utilizing ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J. Pharm. Anal. 2013;3:292–297. doi: 10.1016/j.jpha.2013.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wang CZ, Kim KE, Du GJ, Qi LW, Wen XD, Li P, Bauer BA, Bissonnette MB, Musch MW, Chang EB, Yuan CS. Ultra-Performance Liquid Chromatography and Time-of-Flight Mass Spectrometry Analysis of Ginsenoside Metabolites in Human Plasma. Am. J. Chin. Med. 2011;39:1161–1171. doi: 10.1142/S0192415X11009470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Wang HQ, Guo S, Qian DW, Qian YF, Duan JA. Comparative analysis of quinolizidine alkaloids from different parts of Sophora alopecuroides seeds by UPLC–MS/MS. J. Pharm. Biomed. Anal. 2012;67-68:16–21. doi: 10.1016/j.jpba.2012.04.024. [DOI] [PubMed] [Google Scholar]
  80. Wang L, Yuan K, Yu WW. Studies of UPLC fingerprint for the identification of Magnoliae officinalis cortex processed. Pharmacogn. Mag. 2010;6:83–88. doi: 10.4103/0973-1296.62891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Wang P, Sun H, Lv HT, Sun WJ, Yuan Y, Han Y, Wang DW, Zhang AH, Wang XJ. Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of LiuWei Di Huang Wan detected by UPLC-HDMS. J. Pharm. Biomed. Anal. 2010;53:631–645. doi: 10.1016/j.jpba.2010.04.032. [DOI] [PubMed] [Google Scholar]
  82. Wang XJ, Sun H, Zhang AH, Jiao GZ, Sun WJ, Yuan Y. Pharmacokinetics screening for multi-components absorbed in the rat plasma after oral administration traditional Chinese medicine formula Yin-Chen-Hao-Tang by ultra performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight mass spectrometry combined with pattern recognition methods. Analyst. 2011;136:5068–5076. doi: 10.1039/c1an15752c. [DOI] [PubMed] [Google Scholar]
  83. Wang XJ, Wang HY, Zhang AH, Lu X, Sun H, Dong H, Wang P. Metabolomics Study on the Toxicity of Aconite Root and Its Processed Products Using Ultraperformance Liquid-Chromatography/Electrospray-Ionization Synapt High-Definition Mass Spectrometry Coupled with Pattern Recognition Approach and Ingenuity Pathways Analysis. J. Proteome Res. 2012;11:1284–1301. doi: 10.1021/pr200963e. [DOI] [PubMed] [Google Scholar]
  84. Wang YY, He S, Cheng XC, Lu YX, Zou YP, Zhang QL. UPLC-Q-TOF-MS/MS fingerprinting of Traditional Chinese Formula SiJunZiTang. J. Pharm. Biomed. Anal. 2013;80:24–33. doi: 10.1016/j.jpba.2013.02.021. [DOI] [PubMed] [Google Scholar]
  85. Wang Y, Yao YM, An R, You LS, Wang XH. Simultaneous determination of puerarin, daidzein, baicalin, wogonoside and liquiritin of GegenQinlian decoction in rat plasma by ultra-performance liquid chromatography–mass spectrometry. J. Chromatogr. B. 2009;877:1820–1826. doi: 10.1016/j.jchromb.2009.05.035. [DOI] [PubMed] [Google Scholar]
  86. Waters Corporation Ultra Performance LC™ by design, USA, 720000880EN LL&LW-UL. 2004.
  87. Wen J, Qiao Y, Yang J, Liu XY, Song Y, Liu ZG, Li FM. UPLC–MS/MS determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Si Ni San decoction. J. Pharm. Biomed. Anal. 2012;66:271–277. doi: 10.1016/j.jpba.2012.03.040. [DOI] [PubMed] [Google Scholar]
  88. Wu FF, Sun H, Wei WF, Han Y, Wang P, Dong TW, Yan GL, Wang XJ. Rapid and global detection and characterization of the constituents in ShengMai San by ultra-performance liquid chromatography-high-definition mass spectrometry. J. Sep. Sci. 2011;34:3194–3199. doi: 10.1002/jssc.201100253. [DOI] [PubMed] [Google Scholar]
  89. Wu LB, Jiang X, Huang LF, Chen SL. Processing Technology Investigation of Loquat ( Eriobotrya japonica ) Leaf by Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Combined with Chemometrics. PLoS One. 2013;8:e64178. doi: 10.1371/journal.pone.0064178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Xiong AZ, Yang L, Ji LL, Wang ZY, Yang XJ, Chen Y, Wang XL, Wang CH, Wang ZT. UPLC-MS based metabolomics study on Senecio scandens and S. vulgaris: an approach for the differentiation of two Senecio herbs with similar morphology but different toxicity. Metabolomics. 2012;8:614–623. [Google Scholar]
  91. Xu HY, Zhang YC, Tao Y, Huang B, Shen D, Li G, Yang HJ. Study of chemical fingerprint for Yuanhu Zhitong tablet by UPLC/Q-TOF-MS. J. Liq. Chromatogr. Related Technol. 2013;36:807–820. [Google Scholar]
  92. Xu W, Qiu XH, Zhang J, Zhu DY, Yang YM, Lu CJ. Analysis of saponins in Panax notoginseng by UPLC-LTQ-Orbitrap MS/MS. Yao Xue Xue Bao. 2012;47(6):773–778. [PubMed] [Google Scholar]
  93. Xu YJ, Foubert K, Dhooghe L, Lemière F, Cimanga K, Mesia K, Apers S, Pieters L. Chromatographic profiling and identification of two new iridoid-indole alkaloids by UPLC–MS and HPLC-SPE-NMR analysis of an antimalarial extract from Nauclea pobeguinii. Phytochem. Lett. 2012;5:316–319. [Google Scholar]
  94. Xue CF, Guo JM, Qian DW, Duan JA, Shang EX, Shu Y, Lu YW. Identification of the potential active components of Abelmoschus manihot in rat blood and kidney tissue by microdialysis combined with ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J. Chromatogr. B. 2011;879:317–325. doi: 10.1016/j.jchromb.2010.12.016. [DOI] [PubMed] [Google Scholar]
  95. Yan GL, Sun H, Sun WJ, Zhao L, Meng XC, Wang XJ. Rapid and global detection and characterization of aconitum alkaloids in Yin Chen Si Ni Tang, a traditional Chinese medical formula, by ultra performance liquid chromatography–high resolution mass spectrometry and automated data analysis. J. Pharm. Biomed. Anal. 2010;53:421–431. doi: 10.1016/j.jpba.2010.05.004. [DOI] [PubMed] [Google Scholar]
  96. Yang B, Zhang AH, Sun H, Dong W, Yan GL, Li TL, Wang XJ. Metabolomic study of insomnia and intervention effects of Suanzaoren decoction using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry. J. Pharm. Biomed. Anal. 2012;58:113–124. doi: 10.1016/j.jpba.2011.09.033. [DOI] [PubMed] [Google Scholar]
  97. Yang B, Dong W, Zhang AH, Sun H, Wu FF, Wang P, Wang XJ. Ultra-performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry for rapid analysis of constituents of Suanzaoren decoction. J. Sep. Sci. 2011;34:3208–3215. doi: 10.1002/jssc.201100632. [DOI] [PubMed] [Google Scholar]
  98. Yang SS, Zhang KR, Lin X, Miao YQ, Meng LK, Chen W, Tang X. Pharmacokinetic comparisons of single herb extract of Fufang Danshen preparation with different combinations of its constituent herbs in rats. J. Pharm. Biomed. Anal. 2012;67-68:77–85. doi: 10.1016/j.jpba.2012.03.058. [DOI] [PubMed] [Google Scholar]
  99. Yang X, Wang BC, Zhang X, Yang SP, Li W, Tang Q, Singh GK. Simultaneous determination of nine flavonoids in Polygonum hydropiper L. samples using nanomagnetic powder three-phase hollow fibre-based liquid-phase microextraction combined with ultrahigh performance liquid chromatography-mass spectrometry. J. Pharm. Biomed. Anal. 2011;54:311–316. doi: 10.1016/j.jpba.2010.08.026. [DOI] [PubMed] [Google Scholar]
  100. Yao X, Zhou GS, Tang YP, Qian YF, Guan HL, Pang HQ, Zhu SQ, Mo X, Su SL, Jin C, Qin Y, Qian DW, Duan JA. Simultaneous quantification of flavonol glycosides, terpene lactones, biflavones, proanthocyanidins, and ginkgolic acids in Ginkgo biloba leaves from fruit cultivars by ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry. J. Biomed. Biotechnol. 2013;2013:1–11. doi: 10.1155/2013/582591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Yin QW, Sun H, Zhang AH, Wang XJ. Pharmacokinetics and tissue distribution study of scoparone in rats by ultraperformance liquid-chromatography with tandem high-definition mass spectrometry. Fitoterapia. 2012;83:795–800. doi: 10.1016/j.fitote.2012.03.010. [DOI] [PubMed] [Google Scholar]
  102. Zhang J, Huang ZH, Qiu XH, Yang YM, Zhu DY, Xu W. Neutral fragment filtering for rapid identification of new diester-diterpenoid alkaloids in roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry. PLoS One. 2012;7:e52352. doi: 10.1371/journal.pone.0052352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Zhang J, Jin Y, Dong J, Xiao YS, Feng JT, Xue XY, Zhang XL, Liang XM. Systematic screening and characterization of tertiary and quaternary alkaloids from corydalis yanhusuo W.T. Wang using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Talanta. 2009;78:513–522. doi: 10.1016/j.talanta.2008.12.002. [DOI] [PubMed] [Google Scholar]
  104. Zhang L, Zhu L, Wang YF, Jiang ZZ, Chai X, Zhu Y, Gao XM, Qi AD. Characterization and quantification of major constituents of Xue Fu Zhu Yu by UPLC-DAD-MS/MS. J. Pharm. Biomed. Anal. 2012;62:203–209. doi: 10.1016/j.jpba.2011.12.026. [DOI] [PubMed] [Google Scholar]
  105. Zhang YJ, Huang X, Wang Y, Xie Y, Qiu XJ, Ren P, Gao LC, Zhou HH, Zhang HY, Qiao MQ. Ferulic acid-induced anti-depression and prokinetics similar to Chaihu–Shugan–San via polypharmacology. Brain Res. Bull. 2011;86:222–228. doi: 10.1016/j.brainresbull.2011.07.002. [DOI] [PubMed] [Google Scholar]
  106. Zhang YJ, Huang X, Xie Y, Wang Y, Qiu XJ, Fan R, Ren P, Liu ZQ, Zhou HH. Application of ultra-high performance liquid chromatography (UPLC) with photodiode array detector for the simultaneous determination of 12 chemical components of traditional Chinese Si-Jun-Zi-Tang formula. J. Med. Plants Res. 2011;5:1955–1961. [Google Scholar]
  107. Zheng YL, Chen Y, Ren YP, Luan LJ, Wu YJ. An ultra-pressure liquid chromatography–tandem mass spectrometry method for the simultaneous determination of three physalins in rat plasma and its application to pharmacokinetic study of Physalis alkekengi var. franchetii(Chinese lantern) in rats. J. Pharm. Biomed. Anal. 2012;58:94–101. doi: 10.1016/j.jpba.2011.09.012. [DOI] [PubMed] [Google Scholar]
  108. Zheng YL, Luan LJ, Chen Y, Ren YP, Wu YJ. Characterization of physalins and fingerprint analysis for the quality evaluation of Physalis alkekengi L. var. franchetii by ultra-performance liquid chromatography combined with diode array detection and electrospray ionization tandem mass spectrometry. J. Pharm. Biomed. Anal. 2012;71:54–62. doi: 10.1016/j.jpba.2012.08.020. [DOI] [PubMed] [Google Scholar]
  109. Zheng ZJ, Yan TM, Chen WY, Ye L, Tang L, Liu ZQ. Pharmacokinetic determination of ephedrine in Herba Ephedrae and Wu Tou Tang decoctions in rats using ultra performance liquid chromatography tandem mass spectrometry. Xenobiotica. 2012;42:775–783. doi: 10.3109/00498254.2012.658884. [DOI] [PubMed] [Google Scholar]
  110. Zhao YY, Wang JH, Fu XT, Chen YG, Guo HZ. Simultaneous determination of eleven flavonoid glycosides in Ginkgo biloba leaves collected in different seasons by UPLC PDA method. Acta Pharm. Sinic. 2013;48:98–103. [PubMed] [Google Scholar]
  111. Zhong XL, Guo J, Wang LY, Luo DS, Bei WJ, Chen YY, Yan KQ, Peng JH. Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC–Q–TOF–MS/MS. Chromatographia. 2012;75:111–129. doi: 10.1007/s10337-011-2164-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Zhou DY, Zhang XL, Xu Q, Xue XY, Zhang FF, Liang XM. UPLC/Q-TOFMS/MS as a powerful technique for rapid identification of polymethoxylated flavones in Fructus aurantii. J. Pharm. Biomed. Anal. 2009;50:2–8. doi: 10.1016/j.jpba.2009.03.010. [DOI] [PubMed] [Google Scholar]
  113. Zhu HB, Wang CY, Qi Y, Song FR, Liu ZQ, Liu SY. Fingerprint analysis of Radix Aconiti using ultra-performance liquid chromatography-electrospray ionization/ tandem mass spectrometry (UPLC-ESI/MSn) combined with stoichiometry. Talanta. 2013;103:56–65. doi: 10.1016/j.talanta.2012.10.006. [DOI] [PubMed] [Google Scholar]
  114. Zhu JB, Guo XJ, Fu SP, Zhang XL, Liang XM. Characterization of steroidal saponins in crude extracts from Dioscorea zingiberensis C. H. Wright by ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry. J. Pharm. Biomed. Anal. 2010;53:462–474. doi: 10.1016/j.jpba.2010.05.019. [DOI] [PubMed] [Google Scholar]
  115. Zhu S, Ma CY, Fu QY, Hu LM, Lou ZX, Wang HX, Tao GJ. Application of Ionic Liquids in an Online Ultrasonic Assisted Extraction and Solid-Phase Trapping of Rhodiosin and Rhodionin from Rhodiola roseafor UPLC. Chromatographia. 2013;76:195–200. [Google Scholar]

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