Degradation method for the antiepileptic drug primidone in water using a hybrid high-frequency ultrasound and photo-Fenton process

Abstract

Antiepileptic drugs are considered contaminants of emerging concern in water and are resistant to conventional wastewater treatment processes. Therefore, their presence has been detected in surface waters, and their elimination/degradation requires effective treatment methods. In this research, ultrasound-based methods (e.g., sonolysis, sono-Fenton, and sono-photo-Fenton) were addressed in the degradation of antiepileptic drug primidone at laboratory scale. A high-frequency ultrasound (at 578 kHz and 20.4 W) was applied. Then, Fe²⁺ ions (5 mg l^-1) and a UVA lamp (4 W) were added to the sonochemical reactor. After 75 min of treatment, the sono-photo-Fenton method showed better degradation efficiency (93 %) than the sono-Fenton (83 %) and sonolysis (62 %) methods. Finally, the effectiveness of the degradation method by sono-photo-Fenton was tested in simulated pharmaceutical wastewater, degrading 72 % of primidone at 75 min of treatment, indicating matrix effect plays a role in the degradation (which could be a potential application of ultrasound hybridized with the photo-Fenton process).

• •Three ultrasound-based treatment methods were applied to degrade primidone in water.
• •The sono-photo-Fenton method degraded 93 % of primidone during 75 min of treatment.
• •The matrix influence on primidone degradation by sono-photo-Fenton was evaluated.

Graphical abstract

Specifications table

 

Subject area	Environmental Science
More specific subject area	Water treatment and degradation of organic pollutants.
Name of your method	Degradation method for the antiepileptic drug primidone (Mysoline) in water using a hybrid high-frequency ultrasound and photo-Fenton process.
Name and reference of original method	Kevin Celis-Llamoca, Efraím A. Serna-Galvis, Ricardo A. Torres-Palma, Jessica I. Nieto-Juárez. High-frequency ultrasound processes as alternative methods for degrading meropenem antibiotic in water, MethodsX, 13 (2022),10.1016/j.mex.2022.101835
Resource availability	All resources are detailed within this article.

Background

In recent years, the presence of antiepileptic drugs in surface water sources has been increasing, which is directly related to their growing global consumption [1]. Primidone (PRI), a drug used to control involuntary movements and focal epileptic seizures, has a low metabolism rate in the body. Only 27–36 % of the administered dose is effectively absorbed, while 64–73 % is excreted through urine [2]. Although these drugs play a fundamental role in human health, their presence in water bodies poses a significant environmental risk. Due to their recalcitrant nature, drug primidone and similar compounds are not effectively removed in wastewater treatment plants, which could harm aquatic ecosystems [3,4].

Conventional methods (such as biological processes) have proven ineffective in treating recalcitrant molecules such as pharmaceutical substances. New and efficient treatment methods for their degradation in aquatic systems are needed, such as advanced oxidation processes (AOPs). Diverse AOPs have been studied to eliminate pharmaceuticals from water, including (photo-)Fenton, ozone, heterogeneous photocatalysis, electrochemical oxidation, and MOF catalysts, among others [[5], [6], [7]]. Among these AOP methods, the high-frequency ultrasound process is emerging as a promising option, because it does not require the addition of chemical oxidizing agents, operates under ambient conditions, and is easy to apply. Several studies have demonstrated its effectiveness, especially when combined with complementary AOPs [[8], [9], [10], [11]].

The degradation of recalcitrant contaminants, e.g., the antiepileptic drug primidone, is closely related to the generation of hydroxyl radicals (^•OH) formed by the cleavage of water vapour and oxygen molecules induced by acoustic cavitation (denoted by “)))”) (Eqs. (1)–(4)). In addition, the sonogenerated hydroxyl radicals tend to recombine, leading to the accumulation of hydrogen peroxide molecules (Eq. (5)) [12].

H₂O +))) → ^•H + ^•OH (1)

O₂ +))) → 2 ^•O (2)

H₂O + O^• → 2 ^•OH (3)

O₂ + ^•H → ^•O + ^•OH (4)

2 ^•OH → H₂O₂ (5)

To take advantage of the sonogenerated H₂O₂, ferrous ions (Fe²⁺) can be added to generate the Fenton reaction in situ, thus producing additional OH radicals (Eq. (6)) and the addition of UVA light in the Fenton process enhances the catalytic cycle of the photoreduction of Fe(III) to Fe(II) which produces more OH radicals (Eq. (7)) [13], generating a sono-Fenton and sono-photo-Fenton process, respectively.

Fe²⁺ + H₂O₂ → Fe³⁺ + ^•OH + OH^- (6)

Fe³⁺ + H₂O + hʋ → Fe²⁺ + ^•OH + H⁺ (7)

Due to the potential environmental impact of the antiepileptic drug PRI and the degradation efficiency of hydroxyl radical-based AOP treatment on recalcitrant molecules, this study aims to present a method for the degradation of primidone through the combination of ultrasound and photo-Fenton processes at laboratory scale. The novelty of this study lies in integrating ultrasound-induced H₂O₂ generation with UVA light-assisted Fe³⁺/Fe²⁺ photoreduction, achieving a higher efficiency in the oxidation/degradation of the pollutant without the need for external oxidants or complex catalysts. Futhermore, unlike conventional Fenton processes or sonolysis alone, this hybrid sono-photo-Fenton process enhances the formation of ^•OH through acoustic cavitation and photoactivation to degrade persistent pharmaceuticals.

Method details

Materials

Primidone (PRI) was purchased from Biosynth, Switzerland. Ammonium heptamolybdate tetrahydrate and sodium acetate trihydrate were obtained from J.T. Baker, Spain. Ammonium chloride, monopotassium phosphate, potassium chloride, calcium chloride, sodium chloride, sodium sulfate, and urea were purchased from Merck Peruana S.A. Iron sulfate heptahydrate and catalase (2000–5000 units mg⁻¹) were acquired from Sigma-Aldrich, USA. Hydroxylamine hydrochloride (Thermo Scientific, USA), ortho-phenanthroline (Carlo Erba). Acetonitrile (HPLC grade, Supelco) and potassium iodide (Fisher Chemical, USA) were used.

Equipments

A pH meter (Metrohm 913), a thermocouple (Hanna), a vortex mixer (Scientific Industries), and a UV–VIS spectrophotometer (Easy UV, Mettler Toledo) were used. For the sonochemical system, a glass reactor (500 mL), a multifrequency ultrasound generator, a transducer (Meinhardt Ultrasonics), a thermostat (Brookfield), and a Philips UV-A lamp (F4T5BLB; main emission peak at 365 nm, 4 W) were utilized.

Analytical methods

The ultrasonic batch reactor (containing 300 mL of PRI solution at 2.5 ppm) was utilized at laboratory scale. The temperature of the reactor was controlled at 18 ± 2 °C using a Brookfield thermostat, and the pH of the solution was maintained at 6.2 ± 0.2. The UV-A lamp used in the experiments was placed inside a quartz tube and fixed on a support within the reactor to maintain a constant position throughout all tests. The acoustic power was determined using the calorimetric method [14]. All experiments were conducted in triplicate, and the results were expressed as average values with their respective standard deviations.

For the determination of oxidants, the iodometric method was used. A mixture of 600 µL of filtered sample, 50 µL of ammonium heptamolybdate (0.01 M), and 1350 µL of potassium iodide (0.1 M) was prepared. The solution was homogenized using a vortex mixer, and after 5 min of reaction, the absorbance was measured in a UV spectrophotometer at 350 nm [15].

Finally, the quantitative analysis of PRI was performed using high-performance liquid chromatography (HPLC; Agilent 1100) equipped with a diode array detector (DAD) and a Teknokroma C-18 column (5 µm, ID = 4.6 mm, length = 150 mm), with a mobile phase of acetonitrile: ultrapure water (22:78 % v/v), an injection volume of 20 µL, a flow rate of 0.8 mL/min, and a run time of 15 min at 210 nm. Additionally, 1400 µL aliquots were taken from the sonochemical reactor and placed in a vial containing 100 µL of catalase (200 units/mL) to scavenge the residual hydrogen peroxide.

Method validation

Method for degrading primidone using sonolysis

The sonochemical treatment method (at 578 kHz and 20.4 W) was applied for the PRI degradation (Fig. 1a). After 75 min of treatment, 62 % of PRI was degraded. Its degradation can be attributed mainly to the attack of sonogenerated hydroxyl radicals (^•OH), which is indirectly measured through the accumulation of H₂O₂ (Eq. (5)). In fact, Fig. 1b shows that the H₂O₂ accumulation in the primidone presence was lower than in distilled water (DW) alone. This difference confirms the ability of the sonochemical reactor to produce ^•OH, which leads to primidone degradation.

Fig. 1.

(a) Degradation of primidone (2.5 mg L^-1) by high-frequency ultrasound process at 578 kHz and 20.4 W. (b) Comparison of H₂O₂ accumulation in absence and presence of the antiepileptic drug (T: 18 ± 2 °C, pH: 6.2 ± 0.2).

Method for the degradation of primidone (Mysoline) using sono-Fenton and sono-photo-Fenton

The incorporation of Fe²⁺ ions (5 mg L^-1) alone and together with UV-A lamp (4 W) into the primidone treatment system enabled the activation of the sono-Fenton and sono-photo-Fenton processes, respectively. The evolution of degradation (C/Co) and accumulation of H₂O₂ is shown on Fig. 2. After 75 min of treatment, 83 and 93 % of PRI were degraded by sono-Fenton and sono-photo-Fenton, respectively (Fig. 2a). This improvement can be attributed to the Fenton and photo-Fenton reactions ((6), (7)) that promote the production of additional hydroxyl radicals from the H₂O₂ generated in situ in the sonochemical reactor, improving the degradation of the PRI, which is supported by the low production of H₂O₂ in the sono-photo-Fenton method (Fig. 2b).

Fig. 2.

(a) Degradation of primidone (2.5 mg L^-1) by sono-Fenton and sono-photo-Fenton process (578 kHz, 20.4 W). (b) Comparison of H₂O₂ accumulation in both processes (T: 18 ± 2 °C, pH: 6.2 ± 0.2).

Degradation of primidone in the synthetic pharmaceutical wastewater (SPWW)

Finally, the degradation of PRI in a complex matrix was evaluated. A synthetic pharmaceutical wastewater (SPWW; whose composition was according to [16], and it has as main components urea, chloride, sulfate, and phosphate anions) was considered. Fig. 3 shows the evolution of PRI degradation in SPWW and distilled water (DW) treated by the sono-photo-Fenton method. As can be seen, the degradation in SPWW was lower than DW, degrading 72 % of PRI at 75 min of treatment. This behavior can be attributed to the presence of inorganic anions from complex matrix, such as chloride, phosphate, and sulfate anions, which react with hydroxyl radicals (•OH) [17], forming less reactive oxidizing species during the sono-photo-Fenton method. According to Fig. 3, complete degradation of PRI in SPWW can be achieved considering the kinetic constant (k), whose k value was 0.0172 min^-1, indicating that the time required to degrade 98 % of primidone is estimated at 2 h. This result indicates that hybridized processes could be an alternative method to use in specific applications for the treatment of antiepileptic drugs, even in complex matrices such as those coming from the pharmaceutical industries.

Fig. 3.

Degradation of primidone (2.5 mg L^-1) by sono-photo-Fenton method in distilled water (DW) and simulated pharmaceutical wastewater (SPWW) (f: 578 kHz, p: 20.4 W, lamp: UVA, Fe²⁺: 5 mg L^-1, T: 18 ± 2 °C, pH: 6.2 ± 0.2).

Final remarks

• •The high-frequency ultrasound-based method successfully degrades the antiepileptic primidone.
• •The sono-photo-Fenton method was the most efficient for degrading primidone.
• •The elimination of primidone in SPWW at 98 % was achieved after 2 h by the sono-photo-Fenton method.

Limitations

Not applicable.

Ethics statements

The work does not involve studies with animals and humans.

CRediT authorship contribution statement

Katiusca E. Gonzales–Rivera: Investigation, Methodology, Funding acquisition, Writing – original draft. Jessica I. Nieto-Juárez: Conceptualization, Supervision, Funding acquisition, Resources, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on request.