J. Pharm. Pharmacogn. Res., vol. 14, no. 3, Article ID 2550, May-Jun 2026.

DOI: https://doi.org/10.56499/jppres_14.3.2550

Review

Comparative analysis of chemical toxicological studies of pregabalin in neuropathic pain management (review)

 

[Análisis comparativo de estudios toxicológicos químicos de la pregabalina en el tratamiento del dolor neuropático (revisión)]

 

Nargiz Parkhatkyzy^1*, Alma Shukirbekova¹, Zumrad Usmanalieva², Kundyzay Mirzakir¹, Lyazzat Sagyndykova¹, Nazakat Rakhym¹

 

¹Department of Pharmaceutical Disciplines, Astana Medical University, Astana, Kazakhstan.

²Department of Analytical and Pharmaceutical Chemistry of the Pharmaceutical Institute of Education and Research, Tashkent, Uzbekistan.

*E-mail: nargizparkhatkyzy@gmail.com

 

Abstract

Context: The use of pregabalin in neuropathic pain management has been increasingly associated with concerns regarding toxicity, particularly in cases of overdose, misuse, and co-exposure with central nervous system depressants. In parallel, there is a growing need for reliable analytical methods to quantify pregabalin in biological matrices.

Aims: To systematically evaluate the evidence on toxicological outcomes associated with pregabalin exposure and the analytical methods used for its detection and quantification.

Methods: The literature retrieval process involved searching five electronic databases (PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar) for studies published between 2020 and 2025. Eligible records were screened using predefined criteria, and data were extracted on study design, population characteristics, exposure context, toxicological outcomes, and analytical techniques (e.g., LC–MS/MS, GC–MS, HPLC). Due to heterogeneity across study designs and outcomes, a narrative synthesis was performed.

Results: A total of 20 studies were included, comprising observational clinical toxicology studies, forensic investigations, case reports/series, toxicological surveillance reports, systematic reviews, and analytical validation studies. The available evidence indicates that pregabalin toxicity is primarily characterized by dose-dependent central nervous system depression, with clinical manifestations ranging from mild sedation to severe complications such as coma and respiratory failure. More serious and fatal outcomes were mainly associated with overdose scenarios and concomitant use of other central nervous system depressants. Liquid chromatography–tandem mass spectrometry was the most frequently used analytical technique.

Conclusions: Pregabalin toxicity demonstrates a clear dose- and context-dependent pattern, with increased risk in the presence of co-ingestants and renal impairment. Greater standardization of analytical validation and clinically interpretable concentration thresholds is required to improve consistency in clinical and forensic toxicology.

Keywords: analytical methods; central nervous system depression; LC–MS/MS; overdose; pregabalin; toxicology.

 

 

Resumen

Contexto: El uso de pregabalina en el tratamiento del dolor neuropático se ha asociado cada vez más con preocupaciones sobre su toxicidad, particularmente en casos de sobredosis, uso indebido y coexposición con depresores del sistema nervioso central. Paralelamente, existe una necesidad creciente de métodos analíticos fiables para cuantificar la pregabalina en matrices biológicas.

Objetivos: Evaluar sistemáticamente la evidencia sobre los efectos toxicológicos asociados a la exposición a la pregabalina, así como los métodos analíticos empleados para su detección y cuantificación.

Métodos: La búsqueda bibliográfica abarcó cinco bases de datos electrónicas (PubMed, ScienceDirect, Web of Science, Scopus y Google Scholar) para identificar estudios publicados entre 2020 y 2025. Los registros seleccionados se evaluaron según criterios preestablecidos y se extrajeron datos sobre el diseño del estudio, las características de la población, el contexto de la exposición, los efectos toxicológicos y las técnicas analíticas (p. ej., LC-MS/MS, GC-MS, HPLC). Dada la heterogeneidad de los diseños y resultados de los estudios, se realizó una síntesis narrativa.

Resultados: Se incluyeron 20 estudios, que abarcaron investigaciones clínicas observacionales de toxicología, estudios forenses, informes y series de casos, informes de vigilancia toxicológica, revisiones sistemáticas y estudios de validación analítica. La evidencia disponible indica que la toxicidad de la pregabalina se caracteriza principalmente por una depresión del sistema nervioso central dependiente de la dosis, con manifestaciones clínicas que van desde sedación leve hasta complicaciones graves, como coma e insuficiencia respiratoria. Los desenlaces más graves y mortales se asociaron principalmente con sobredosis y con el uso concomitante de otros depresores del sistema nervioso central. La técnica analítica utilizada con mayor frecuencia fue la cromatografía líquida acoplada a espectrometría de masas en tándem (LC-MS/MS).

Conclusiones: : La toxicidad de la pregabalina muestra un patrón claro dependiente de la dosis y del contexto, con un riesgo incrementado en presencia de coingestas y deterioro de la función renal. Se requiere una mayor estandarización de la validación analítica y de los umbrales de concentración clínicamente interpretables para mejorar la coherencia en los ámbitos de la toxicología clínica y forense.

Palabras Clave: depresión del sistema nervioso central; LC-MS/MS; métodos analíticos; pregabalina; sobredosis; toxicología.

 

 

https://jppres.com/jppres/pdf/vol14/jppres_14.3.2550.pdf

 

 

Citation Format: Parkhatkyzy N, Shukirbekova A, Usmanalieva Z, Mirzakir K, Sagyndykova L, Rakhym N (2026) Comparative analysis of chemical toxicological studies of pregabalin in neuropathic pain management (review). J Pharm Pharmacogn Res 14(3): 2550. https://doi.org/10.56499/jppres_14.3.2550

 

References

Alelwani W, Alkhazindar A, Alqumaysh B, Kutbi D, Tayeb R, Altobaiqi R (2021) Pregabalin abuse and toxicity and related factors. Int Res J Med Med Sci 9(1): 34–42. https://doi.org/10.30918/IRJMMS.91.21.015

Almalki AH, Ali NA, Elroby FA, El Ghobashy MR, Emam AA, Naguib IA (2021) ESI-LC-MS/MS for therapeutic drug monitoring of binary mixture of pregabalin and tramadol: human plasma and urine applications. Separations 8(2): 21. https://doi.org/10.3390/separations8020021

Antunovic M, Dzudovic J, Kilibarda V, Vučinić S, Đorđević SB (2024) Validation of the rapid and simple LC-MS/MS method for the quantification of pregabalin in plasma of acutely poisoned patients. AChrom 36: 106–113. https://doi.org/10.1556/1326.2023.01104

Bouchard J, Yates C, Calello DP, Gosselin S, Roberts DM, Lavergne V, Hoffman RS, Ostermann M, Peng A, Ghannoum M, EXTRIP Workgroup (2022) Extracorporeal treatment for gabapentin and pregabalin poisoning: systematic review and recommendations from the EXTRIP Workgroup. Am J Kidney Dis 79(1): 88–104. https://doi.org/10.1053/j.ajkd.2021.06.027

Buttram ME, Kurtz SP (2020) Preliminary evidence of pregabalin misuse among prescription and/or illicit opioid (mis)users. J Psychoactive Drugs 52(2): 172–175. https://doi.org/10.1080/02791072.2020.1734695

Carter EJR, Rine NI, Kistamgari S, Hays HL, Spiller HA, Yang J, Zhu M, Smith GA (2024) Gabapentin and pregabalin exposures reported to United States poison centers, 2012-2024. Inj Epidemiol 11: 59. https://doi.org/10.1186/s40621-024-00547-9

Hamid MAA, Elagamy SH, Gamal A, Mansour FR (2024) Eco-friendly cobalt-doped carbon quantum dots for spectrofluorometric determination of pregabalin in pharmaceutical capsules. J Pharm Biomed Anal 248: 116270. https://doi.org/10.1016/j.jpba.2024.116270

Huddleston WR, Robert Lyness J, Quinn A (2024) Review of the demographic factors and toxicology related to deaths due to pregabalin in Northern Ireland. J Forensic Leg Med 101: 102635. https://doi.org/10.1016/j.jflm.2023.102635

Isoardi KZ, Polkinghorne G, Harris K, Isbister GK (2020) Pregabalin poisoning and rising recreational use: A retrospective observational series. Br J Clin Pharmacol 86(12): 2435–2440. https://doi.org/10.1111/bcp.14348

Kalk NJ, Chiu CT, Sadoughi R, Baho H, Williams BD, Taylor D, Copeland CS.  (2022) Fatalities associated with gabapentinoids in England (2004-2020). Br J Clin Pharmacol: 88(8): 3911–3917. https://doi.org/10.1111/bcp.15352

Kaye AD, Armistead G, Amedio LS, Manthei ME, Ahmadzadeh S, Bernhardt B, Shekoohi S (2025) Evolving treatment strategies for neuropathic pain: a narrative review. Medicina 61(6): 1063. https://doi.org/10.3390/medicina61061063

Kriikku P, Ojanperä I (2021) Pregabalin and gabapentin in non-opioid poisoning deaths. Forensic Sci Int 324: 110830. https://doi.org/10.1016/j.forsciint.2021.110830

Malviya NJ, Alqarni M, Alshehri AA, Obaydo RH, Varu HL (2025) Evolution of pregabalin analytical methods: a comprehensive assessment of performance, accessibility, and future directions. Crit Rev Anal Chem 1–21. https://doi.org/10.1080/10408347.2025.2546538

Naguib IA, Ali NA, Elroby FA, Elghobashy MR (2021) Green HPLC-DAD and HPTLC methods for quantitative determination of binary mixture of pregabalin and amitriptyline used for neuropathic pain management. J Chromatogr Sci 59(6): 536–547. https://doi.org/10.1093/chromsci/bmab031

Nahar LK, Paterson S (2025) Pregabalin concentrations: establishing 'normal' and 'cause for concern' concentration ranges in postmortem blood. J Anal Toxicol 49(4): 272–279. https://doi.org/10.1093/jat/bkaf005

Nielsen VT, Wijayasinghe N, Høgberg LCG, Bøgevig S (2023) Case report: a comatose patient with pregabalin overdose successfully treated with continuous renal replacement therapy. Front Med (Lausanne) 10: 1125653. https://doi.org/10.3389/fmed.2023.1125653

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol 134: 178–189. https://doi.org/10.1016/j.jclinepi.2021.03.001

Pelissier-Alicot AL, Fabresse N, Sastre C, Baillif-Couniou V, Becam J, Leonetti G (2022) Death related to the combination of pregabalin and other drugs of abuse: about two cases. Toxicol Anal Clin 34 (Suppl 3): S133. https://doi.org/10.1016/j.toxac.2022.06.259

Rietjens SJ, Sikma MA, Hunault CC, de Lange DW, Hondebrink L (2022) Pregabalin poisoning: evaluation of dose-toxicity relationship. Br J Clin Pharmacol 88(3): 1288–1297. https://doi.org/10.1111/bcp.15073

Shah J, Kotadiya R, Patel R (2022) Analytical Quality by Design-Based robust RP-HPLC method for quantitative estimation of pregabalin and etoricoxib in fixed-dose combination tablet formulation. J AOAC Int 105(6): 1536–1547. https://doi.org/10.1093/jaoacint/qsac082

Thompson A, Morey S, Griffiths A (2020) Pregabalin and its involvement in coronial cases. J Anal Toxicol 44(1): 29–35. https://doi.org/10.1093/jat/bkz041

Thompson I, Gadsby Z, Martin J, Thompson M, Tse R (2024) Gabapentinoid detection in coronial casework in Gold Coast, Australia: a 5-year retrospective study. Forensic Sci Med Pathol 20(3): 847–851. https://doi.org/10.1007/s12024-023-00694-3

Vujović M, Kostić E, Pančić D, Milosavljević B, Stojanović I, Karadžić R, Ilić G (2021) Pregabalin determination in postmortem samples and toxicological significance in forensic cases. Acta Med Medianae 60(3): 5–10. https://doi.org/10.5633/amm.2021.0301

Zhai W, Liu H, Li J, Xin H (2024) Pregabalin-induced rhabdomyolysis: a case series and literature analysis. J Int Med Res 52(6): 3000605241257776. https://doi.org/10.1177/03000605241257776

© 2026 Journal of Pharmacy & Pharmacognosy Research