Valproic acid extraction methods in human samples using gas chromatography: a review

Juliana Blume de  Oliveira; Bruno Pereira dos  Santos; Marcelo Dutra Arbo

doi:10.22456/2527-2616.138963

Authors

Juliana Blume de Oliveira Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Bruno Pereira dos Santos Programa de Pós-Graduação em Ciências da Saúde - Universidade Federal de Ciências da Saúde de Porto Alegre; Faculdade de Farmácia, Departamento de Análises - Universidade Federal do Rio Grande do Sul https://orcid.org/0000-0002-7624-5966
Marcelo Dutra Arbo Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Departamento de Análises - Universidade Federal do Rio Grande do Sul

DOI:

https://doi.org/10.22456/2527-2616.138963

Keywords:

Valproic acid, extraction methods, gas chromatography, sample preparation

Abstract

Valproic acid (VPA) is widely used as an important drug for the treatment of epilepsy, seizures, bipolar disorders, and migraines. However, its narrow therapeutic range lead to risks of unintentional poisoning and potential suicide. Symptoms of VPA intoxication include drowsiness, hyperactivity, confusion, ataxia, coma, and sometimes can mimic brain death. Severe cases necessitate intensive care observation and evaluation of blood/plasma concentrations to determine the severity of poisoning. Analytical methods are crucial for monitoring drugs in biological fluids. This review aimed to describe the extraction methods used for the analysis of VPA in human biological samples using gas chromatography. Among 19 studies reviewed, liquid-liquid extraction (LLE), liquid phase microextraction (LPME), and solid-phase microextraction (SPME) are the most used extraction methods. Considering the laborious nature and large sample volumes required for LLE and solid-phase extraction (SPE), more efficient microextraction methods are needed. LPME, dispersive liquid-liquid microextraction (DLLME), air-assisted liquid-liquid microextraction (AALLME), and others offer promising alternatives. LPME, in particular, is favored ecologically due to reduced solvent usage compared to LLE. Novel approaches like dried blood spots (DBS) present emerging options for sample collection, helping in analytical and therapeutic monitoring contexts. Selection of extraction protocol hinges on method objectives, sample type, and laboratory capacity.

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References

Meyer MR, Welter J, Weber AA, Maurer HH. Development, Validation, and Application of a Fast and Simple GC–MS Method for Determination of Some Therapeutic Drugs Relevant in Emergency Toxicology. Ther Drug Monit. 2011; 33:649–653.

Guo MZ, Shao L, Chen X, Li HJ, Wang L, Pan YJ, et al. Assay of dried blood spot from finger prick for sodium valproate via ink auxiliary headspace gas chromatography mass spectrometry. J Chromatogr A. 2019 Sep 13; 1601:335–339.

Deng C, Li N, Ji J, Yang B, Duan G, Zhang X. Development of water-phase derivatization followed by solid-phase microextraction and gas chromatography/mass spectrometry for fast determination of valproic acid in human plasma. Rapid Commun Mass Spectrom. 2006; 20(8):1281– 1287.

Lipska K, Gumieniczek A, Pietraś R, Filip AA. HPLC-UV and GC-MS Methods for Determination of Chlorambucil and Valproic Acid in Plasma for Further Exploring a New Combined Therapy of Chronic Lymphocytic Leukemia. Molecules. 2021 May 13; 26(10):2903.

Leis HJ, Windischhofer W, Rechberger GN, Fauler G. Synthesis of [18O2]valproic acid and its use as an internal standard for the quantitative measurement by gas chromatography–electron ionization mass spectrometry. Journal of Chromatography B. 2003; 784:69–75.

Chateauvieux S, Morceau F, Dicato M, Diederich M. Molecular and therapeutic potential and toxicity of valproic acid. Journal of Biomedicine and Biotechnology. 2010 Jul 29; 2010.

Fazeli-Bakhtiyari R, Panahi-Azar V, Sorouraddin MH, Jouyban A. Determination of valproic acid in human plasma using dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection. Iranian Journal of Basic Medical Sciences. 2015; 18(10):979-988.

Shahdousti P, Mohammadi A, Alizadeh N. Determination of valproic acid in human serum and pharmaceutical preparations by headspace liquidphase microextraction gas chromatography-flame ionization detection without prior derivatization. Journal of Chromatography B. 2007 May 1; 850(1- 2):128–133.

Jain R, Gupta MK, Chauhan A, Pandey V, Reddy Mudiam MK. Ultrasound-assisted dispersive liquidliquid microextraction followed by GC-MS/MS analysis for the determination of valproic acid in urine samples. Bioanalysis. 2015 Oct; 7(19):2451–2459.

Schaefer VD, de Lima Feltraco Lizot L, Hahn RZ, Schneider A, Antunes MV, Linden R. Simple determination of valproic acid serum concentrations using BioSPME followed by gas chromatographymass spectrometric analysis. Journal of Chromatography B. 2021 Mar 15; 1167:122574.

Feriduni B, Barzegar M, Sadeghvand S, Shiva S, Khoubnasabjafari M, Jouyban A. Determination of valproic acid and 3-heptanone in plasma using airassisted liquid-liquid microextraction with the assistance of vortex: Application in the real samples. Bioimpacts. 2019 Mar 8; 9(2):105–113.

Rhoden L, Antunes MV, Hidalgo P, Álvares da Silva C, Linden R. Simple procedure for determination of valproic acid in dried blood spots by gas chromatography-mass spectrometry. J Pharm Biomed Anal. 2014 Aug 5; 96:207–212.

Gu X, Yu S, Peng Q, Ma M, Hu Y, Zhou B. Determination of unbound valproic acid in plasma using centrifugal ultrafiltration and gas chromatography:Application in TDM. Anal Biochem. 2020 Jan 1; 588:113475.

Farajzadeh MA, Farhadi K, Matin AA, Hashemi P, Jouyban A. Headspace solid-phase microextractiongas chromatography method for the determination of valproic acid in human serum, and formulations using hollow-fiber coated wire. Anal Sci. 2009 Jul; 25(7):875–879.

Khatibi, S. A., Hamidi, S., & Siahi-Shadbad, M. R. (2022). Application of liquid-liquid extraction for the determination of antibiotics in the foodstuff: recent trends and developments. Critical reviews in analytical chemistry, 52(2), 327-342.

Koller MF, Schmid M, Iten PX, Vonlanthen B, Bär W. Fatal intoxication with naftidrofuryl. Leg Med. 2009 Sep; 11(5):229–233.

Namera, A., Uekusa, K., Saito, T., Yoshimoto, K., Ishiuchi, N., Murata, K., & Nagao, M. (2022). A method for determining valproic acid in human whole blood and urine via gas chromatography-mass spectrometry and small-scale inter-laboratory trial. Legal Medicine, 59, 102133.

Aly, A. A., & Górecki, T. (2020). Green approaches to sample preparation based on extraction techniques. Molecules, 25(7), 1719.

Stephenson JB, Flater ML, Bain LT. Analysis of Valproic Acid, Salicylic Acid and Ibuprofen in Whole Blood by GC-MS. J Anal Toxicol. 2016 Oct; 40(8):649–652.

Farajzadeh MA, Mogaddam MRA. Air-assisted liquid-liquid microextraction method as a novel microextraction technique; application in extraction and preconcentration of phthalate esters in aqueous sample followed by gas chromatography-flame ionization detection. Anal Chim Acta. 2012 May 30; 728:31–38.

Birk L, dos Santos BP, Schwarz P de S, Eller S, de Oliveira TF. Green chemistry: Developments and perspectives for sample treatment in forensic methodologies. WIREs Forensic Science. 2023 Nov; 5(6).

Matin AA, Biparva P, Amanzadeh H, Farhadi K. Zinc/Aluminum layered double hydroxide-titanium dioxide composite nanosheet film as novel solid phase microextraction fiber for the gas chromatographic determination of valproic acid. Talanta. 2013 Jan 15; 103:207–13.

Mizuno S, Lee XP, Fujishiro M, Matsuyama T, Yamada M, Sakamoto Y, et al. High-throughput determination of valproate in human samples by modified QuEChERS extraction and GC-MS/MS. Leg Med. 2018 Mar; 31:66–73.

Ikeda, K., Ikawa, K., Yokoshige, S., Yoshikawa, S., & Morikawa, N. (2014). Gas chromatography–electron ionization–mass spectrometry quantitation of valproic acid and gabapentin, using dried plasma spots, for therapeutic drug monitoring in in‐home medical care. Biomedical Chromatography, 28(12), 1756-1762.

Lee, M. K., & Jung, M. Y. (2023). A highly efficient strategy for simultaneous analysis of eleven monomeric hydroxylated-stilbenes in grape wines and juices by a salting-out assisted liquid–liquid (SALLE) extraction combined with a high-performance liquid chromatography-tandem mass spectrometry (HPLCMS/MS). Food Chemistry, 426, 136661.

Tang, Y. Q., & Weng, N. (2013). Salting-out assisted liquid–liquid extraction for bioanalysis. Bioanalysis, 5(12), 1583-1598.

Shnayder, N. A., Grechkina, V. V., Khasanova, A. K., Bochanova, E. N., Dontceva, E. A., Petrova, M. M., ... & Nasyrova, R. F. (2023). Therapeutic and toxic effects of valproic acid metabolites. Metabolites, 13(1), 134.