{"id":20836,"date":"2026-07-04T20:36:41","date_gmt":"2026-07-05T00:36:41","guid":{"rendered":"https:\/\/jppres.com\/jppres\/?p=20836"},"modified":"2026-08-20T15:55:57","modified_gmt":"2026-08-20T19:55:57","slug":"chemical-toxicological-studies-of-pregabalin","status":"publish","type":"post","link":"https:\/\/jppres.com\/jppres\/chemical-toxicological-studies-of-pregabalin\/","title":{"rendered":"Chemical toxicological studies of pregabalin"},"content":{"rendered":"

J. Pharm. Pharmacogn. Res., vol. 14, no. 3, Article ID 2550, May-Jun 2026<\/strong>.<\/p>\r\n\r\n\r\n\r\n

DOI: https:\/\/doi.org\/10.56499\/jppres_14.3.2550<\/a><\/p>\r\n\r\n\r\n\r\n

Review<\/strong><\/p>\r\n\r\n\r\n\r\n

Comparative analysis of chemical toxicological studies of pregabalin in neuropathic pain management (review)<\/h1>\r\n\r\n

 <\/p>\r\n\r\n

[An\u00e1lisis comparativo de estudios toxicol\u00f3gicos qu\u00edmicos de la pregabalina en el tratamiento del dolor neurop\u00e1tico (revisi\u00f3n)]<\/h2>\r\n\r\n

 <\/p>\r\n\r\n

Nargiz Parkhatkyzy1*<\/sup>, Alma Shukirbekova1<\/sup>, Zumrad Usmanalieva2<\/sup>, Kundyzay Mirzakir1<\/sup>, Lyazzat Sagyndykova1<\/sup>, Nazakat Rakhym1<\/sup><\/h3>\r\n\r\n

 <\/p>\r\n\r\n

1<\/sup>Department of Pharmaceutical Disciplines, Astana Medical University, Astana, Kazakhstan.<\/p>\r\n

2<\/sup>Department of Analytical and Pharmaceutical Chemistry of the Pharmaceutical Institute of Education and Research, Tashkent, Uzbekistan.<\/p>\r\n

*E-mail: nargizparkhatkyzy@gmail.com<\/a><\/p>\r\n\r\n

 <\/p>\r\n\r\n

Abstract<\/strong><\/p>\r\n\r\n\r\n\r\n

Context<\/em>: 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.<\/p>\r\n

Aims<\/em>: To systematically evaluate the evidence on toxicological outcomes associated with pregabalin exposure and the analytical methods used for its detection and quantification.<\/p>\r\n

Methods<\/em>: 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\u2013MS\/MS, GC\u2013MS, HPLC). Due to heterogeneity across study designs and outcomes, a narrative synthesis was performed.<\/p>\r\n

Results<\/em>: 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\u2013tandem mass spectrometry was the most frequently used analytical technique.<\/p>\r\n

Conclusions<\/em>: 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.<\/p>\r\n

Keywords<\/em>: analytical methods; central nervous system depression; LC\u2013MS\/MS; overdose; pregabalin; toxicology.<\/p>\r\n\r\n

 <\/p>\r\n\r\n

\"PDF<\/a><\/figure>\r\n\r\n

 <\/p>\r\n\r\n

Resumen<\/h4>\r\n\r\n\r\n\r\n

Contexto<\/em>: El uso de pregabalina en el tratamiento del dolor neurop\u00e1tico se ha asociado cada vez m\u00e1s con preocupaciones sobre su toxicidad, particularmente en casos de sobredosis, uso indebido y coexposici\u00f3n con depresores del sistema nervioso central. Paralelamente, existe una necesidad creciente de m\u00e9todos anal\u00edticos fiables para cuantificar la pregabalina en matrices biol\u00f3gicas.<\/p>\r\n

Objetivos<\/em>: Evaluar sistem\u00e1ticamente la evidencia sobre los efectos toxicol\u00f3gicos asociados a la exposici\u00f3n a la pregabalina, as\u00ed como los m\u00e9todos anal\u00edticos empleados para su detecci\u00f3n y cuantificaci\u00f3n.<\/p>\r\n

M\u00e9todos:<\/em> La b\u00fasqueda bibliogr\u00e1fica abarc\u00f3 cinco bases de datos electr\u00f3nicas (PubMed, ScienceDirect, Web of Science, Scopus y Google Scholar) para identificar estudios publicados entre 2020 y 2025. Los registros seleccionados se evaluaron seg\u00fan criterios preestablecidos y se extrajeron datos sobre el dise\u00f1o del estudio, las caracter\u00edsticas de la poblaci\u00f3n, el contexto de la exposici\u00f3n, los efectos toxicol\u00f3gicos y las t\u00e9cnicas anal\u00edticas (p. ej., LC-MS\/MS, GC-MS, HPLC). Dada la heterogeneidad de los dise\u00f1os y resultados de los estudios, se realiz\u00f3 una s\u00edntesis narrativa.<\/p>\r\n

Resultados<\/em>: Se incluyeron 20 estudios, que abarcaron investigaciones cl\u00ednicas observacionales de toxicolog\u00eda, estudios forenses, informes y series de casos, informes de vigilancia toxicol\u00f3gica, revisiones sistem\u00e1ticas y estudios de validaci\u00f3n anal\u00edtica. La evidencia disponible indica que la toxicidad de la pregabalina se caracteriza principalmente por una depresi\u00f3n del sistema nervioso central dependiente de la dosis, con manifestaciones cl\u00ednicas que van desde sedaci\u00f3n leve hasta complicaciones graves, como coma e insuficiencia respiratoria. Los desenlaces m\u00e1s graves y mortales se asociaron principalmente con sobredosis y con el uso concomitante de otros depresores del sistema nervioso central. La t\u00e9cnica anal\u00edtica utilizada con mayor frecuencia fue la cromatograf\u00eda l\u00edquida acoplada a espectrometr\u00eda de masas en t\u00e1ndem (LC-MS\/MS).<\/p>\r\n

Conclusiones<\/em>: : La toxicidad de la pregabalina muestra un patr\u00f3n claro dependiente de la dosis y del contexto, con un riesgo incrementado en presencia de coingestas y deterioro de la funci\u00f3n renal. Se requiere una mayor estandarizaci\u00f3n de la validaci\u00f3n anal\u00edtica y de los umbrales de concentraci\u00f3n cl\u00ednicamente interpretables para mejorar la coherencia en los \u00e1mbitos de la toxicolog\u00eda cl\u00ednica y forense.<\/p>\r\n\r\n\r\n\r\n

Palabras Clave<\/em>: depresi\u00f3n del sistema nervioso central; LC-MS\/MS; m\u00e9todos anal\u00edticos; pregabalina; sobredosis; toxicolog\u00eda.<\/p>\r\n\r\n

 <\/p>\r\n\r\n

\"PDF<\/a><\/figure>\r\n

 <\/p>\r\n

\r\n
https:\/\/jppres.com\/jppres\/pdf\/vol14\/jppres_14.3.2550.pdf<\/a><\/div>\r\n
\u00a0<\/div>\r\n
\u00a0<\/div>\r\n<\/figure>\r\n\r\n
Citation Format: <\/strong>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<\/a><\/pre>\r\n\r\n
 <\/p>\r\n\r\n
References<\/h5>\r\n\r\n\r\n\r\n
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\u201342. https:\/\/doi.org\/10.30918\/IRJMMS.91.21.015<\/a><\/p>\r\n
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<\/a><\/p>\r\n
Antunovic M, Dzudovic J, Kilibarda V, Vu\u010dini\u0107 S, \u0110or\u0111evi\u0107 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\u2013113. https:\/\/doi.org\/10.1556\/1326.2023.01104<\/a><\/p>\r\n
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\u2013104. https:\/\/doi.org\/10.1053\/j.ajkd.2021.06.027<\/a><\/p>\r\n
Buttram ME, Kurtz SP (2020) Preliminary evidence of pregabalin misuse among prescription and\/or illicit opioid (mis)users. J Psychoactive Drugs 52(2): 172\u2013175. https:\/\/doi.org\/10.1080\/02791072.2020.1734695<\/a><\/p>\r\n
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<\/a><\/p>\r\n
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<\/a><\/p>\r\n
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<\/a><\/p>\r\n
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\u20132440. https:\/\/doi.org\/10.1111\/bcp.14348<\/a><\/p>\r\n
Kalk NJ, Chiu CT, Sadoughi R, Baho H, Williams BD, Taylor D, Copeland CS.\u00a0 (2022) Fatalities associated with gabapentinoids in England (2004-2020). Br J Clin Pharmacol: 88(8): 3911\u20133917. https:\/\/doi.org\/10.1111\/bcp.15352<\/a><\/p>\r\n
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<\/a><\/p>\r\n
Kriikku P, Ojanper\u00e4 I (2021) Pregabalin and gabapentin in non-opioid poisoning deaths. Forensic Sci Int 324: 110830. https:\/\/doi.org\/10.1016\/j.forsciint.2021.110830<\/a><\/p>\r\n
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\u201321. https:\/\/doi.org\/10.1080\/10408347.2025.2546538<\/a><\/p>\r\n
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\u2013547. https:\/\/doi.org\/10.1093\/chromsci\/bmab031<\/a><\/p>\r\n
Nahar LK, Paterson S (2025) Pregabalin concentrations: establishing ‘normal’ and ’cause for concern’ concentration ranges in postmortem blood. J Anal Toxicol 49(4): 272\u2013279. https:\/\/doi.org\/10.1093\/jat\/bkaf005<\/a><\/p>\r\n
Nielsen VT, Wijayasinghe N, H\u00f8gberg LCG, B\u00f8gevig 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<\/a><\/p>\r\n
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, Hr\u00f3bjartsson 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\u2013189. https:\/\/doi.org\/10.1016\/j.jclinepi.2021.03.001<\/a><\/p>\r\n
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<\/a><\/p>\r\n
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\u20131297. https:\/\/doi.org\/10.1111\/bcp.15073<\/a><\/p>\r\n
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\u20131547. https:\/\/doi.org\/10.1093\/jaoacint\/qsac082<\/a><\/p>\r\n
Thompson A, Morey S, Griffiths A (2020) Pregabalin and its involvement in coronial cases. J Anal Toxicol 44(1): 29\u201335. https:\/\/doi.org\/10.1093\/jat\/bkz041<\/a><\/p>\r\n
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\u2013851. https:\/\/doi.org\/10.1007\/s12024-023-00694-3<\/a><\/p>\r\n
Vujovi\u0107 M, Kosti\u0107 E, Pan\u010di\u0107 D, Milosavljevi\u0107 B, Stojanovi\u0107 I, Karad\u017ei\u0107 R, Ili\u0107 G (2021) Pregabalin determination in postmortem samples and toxicological significance in forensic cases. Acta Med Medianae 60(3): 5\u201310. https:\/\/doi.org\/10.5633\/amm.2021.0301<\/a><\/p>\r\n
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<\/a><\/p>\r\n
\u00a9 2026 Journal of Pharmacy & Pharmacognosy Research<\/p>","protected":false},"excerpt":{"rendered":"
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)   [An\u00e1lisis comparativo de estudios toxicol\u00f3gicos qu\u00edmicos de la pregabalina en el tratamiento del dolor neurop\u00e1tico (revisi\u00f3n)]   Nargiz Parkhatkyzy1*, Alma Shukirbekova1, Zumrad Usmanalieva2, Kundyzay Mirzakir1, … Continue reading Chemical toxicological studies of pregabalin<\/span> →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[37],"tags":[],"class_list":["post-20836","post","type-post","status-publish","format-standard","hentry","category-pharmaceutical-science"],"brizy_media":[],"_links":{"self":[{"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/posts\/20836","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/comments?post=20836"}],"version-history":[{"count":0,"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/posts\/20836\/revisions"}],"wp:attachment":[{"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/media?parent=20836"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/categories?post=20836"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/jppres.com\/jppres\/wp-json\/wp\/v2\/tags?post=20836"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}