Бензодиазепины: классификация, свойства, количественное определение и мониторинг


DOI: https://dx.doi.org/10.18565/pharmateca.2023.9-10.174-180

Кузьмин И.И., Кравцова О.Ю., Платова А.И., Мирошниченко И.И.

1) Научный центр психического здоровья, Москва, Россия; 2) НИИ фармакологии им. В.В. Закусова, Москва, Россия
В обзорной статье описаны общие характеристики и классификация бензодиазепинов (БЗД), методы количественного определения и область их применения. Разобраны воздействие БЗД на рецепторы γ-аминомасляной кислоты и вопросы безопасности их применения. Приводятся сведения по фармакологии, метаболизму и фармакогенетике БЗД. Представлены скрининговые и количественные способы определения БЗД, включая методы экстракции. В сравнительном аспекте описаны основные методы количественного определения БЗД: иммуноферментный анализ и высокоэффективная жидкостная хроматография с масс-спектрометрией.

Литература


1. Peng L., Morford K.L., Levander X.A. Benzodiazepines and Related Sedatives. Med Clin North Am. 2022;106(1):113–29. Doi: 10.1016/j.mcna.2021.08.012.


2. Herzberg D. Happy Pills in America: From Miltown to Prozac. Baltimore, Johns Hopkins University Press. 2009. 279 р.


3. Edinoff A.N., Nix C.A., et al. Benzodiazepines: Uses, Dangers, and Clinical Considerations. Neurol Int. 2021;13:594–607. Doi: 10.3390/neurolint13040059.


4. Скрябин В.Ю., Застрожин М.С., Брюн Е.А., Сычев Д.А. Бензодиазепиновые транквилизаторы как «золотой стандарт» лечения пациентов с синдромом отмен алкоголя. Современная терапия психических расстройств. 2020;1:21–8.


5. Tiglao S.M., Meisenheimer E.S., Oh R.C. Alcohol Withdrawal Syndrome: Outpatient Management. Am. Fam. Physician. 2021;104(3):253–62.


6. Szatkowska P., Koba M., Koslinski P., et al. Analytical methods for determination of benzodiazepines. A short review. Cent Eur J Chem. 2014;12(10):994–1007. Doi: 10.2478/s11532-014-0551-1.


7. Dubovsky S.L., Marshall D. Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice. Psychother Psychosom. 2022;91:307–34. Doi: 10.1159/000524400.


8. Saari T.I., Uusi-Oukari M., Ahonen J., Olkkola K.T. Enhancement of GABAergic activity: neuropharmacological effects of benzodiazepines and therapeutic use in anesthesiology. Pharmacol Rev. 2011;1(63):243 67.


9. Appenzeller B.M.R., Schneider S., Yegles, M.A., et al. Drugs and chronic 812 alcohol abuse in drivers. Forensic Sci Int. 2005;155:83–90.


10. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol. 2012;77:2:295–301. Doi: 10.1111/j.1365-2125.2012.04418.x.


11. Hiemke C., Bergemann N., Clement H., et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsych. 2018;51(01/02):9–62. Doi: 10.1055/s-0043-116492.


12. Xu C., Li C. Y.-T., Kong A.-N.T. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res. 2005;3(28):249 68.


13. Dinis-Oliveira R.J. Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects. Drug Metab Rev. 2017;49(4):451–63.


14. Mei V., Concheiro M., Pardi J., Cooper, G. Validation of an LC-MS/MS Method for the Quantification of 13 Designer Benzodiazepines in Blood. J Analyt Toxicol. 2019;43(9):688–95. Doi: 10.1093/jat/bkz063.


15. Samanidou V., Kaltzi I., Kabir A., Furton K.G. Simplifying sample preparation using fabric phase sorptive extraction technique for the determination of benzodiazepines in blood serum by high-performance liquid chromatography. Biomed. Chromatography. 2016;30(6):829–36.


16. Bajaj A.O., Ly D., Johnson-Davis K.L. Retrospective analysis of metabolite patterns of clobazam and N-desmethylclobazam in human plasma by LC-MS/MS. J Mass Spectrom Adv Clin Lab. 2022;24:100–6. Doi: 10.1016/j.jmsacl.2022.04.005.


17. DeFreitas L., Fonseca Pego A.M., Kronstrand R., et al. Fast and Sensitive Method for the Determination of 17 Designer Benzodiazepines in Hair by Liquid Chromatography-Tandem Mass Spectrometry. J Anal Toxicol. 2022;46(8):852–59. Doi: 10.1093/jat/bkac044.


18. Persona K., Madej K., Knihnicki P., Piekoszewski W. Analytical methodologies for the determination of benzodiazepines in biological samples. J Pharmaceut Biomed Anal. 2015;113:239–64. Doi: 10.1016/j.jpba.2015.02.017.


19. Ahmad S.M., Nogueira J.M.F. High throughput bar adsorptive microextraction: A novel cost-effective tool for monitoring benzodiazepines in large number of biological samples. Talanta. 2019;199:195–202. Doi: 10.1016/j.talanta.2019.02.004.


20. Mastrovito R.A., Papsun D.M., Logan B.K. The Development and Validation of a Novel Designer Benzodiazepines Panel by LC-MS-MS. J Anal Toxicol. 2021;45(5):423–28. Doi: 10.1093/jat/bkab013.


21. Sofalvi S., Lavins E.S, Kaspar C.K., et al. Development and Validation of an LC–MS-MS Method for the Detection of 40 Benzodiazepines and Three Z-Drugs in Blood and Urine by Solid-Phase Extraction. J Analyt Toxicol. 2020:1–10. Doi: 10.1093/jat/bkaa072.


22. Мирошниченко И.И., Шилов Ю.Е. Анализ биологических образцов в современной лабораторной практике. Разработка и регистрация лекарственных средств. 2019;8(2)8:115–20.


23. An J., Dong Z., Zhang W., et al. Development of a simple nanofiber-based solid phase extraction procedure coupled with high performance liquid chromatography analysis for the quantification of eight sedative-hypnotic drugs in human urine samples. Microchem J. 2021;168(27):106475. Doi: 10.1016/j.microc.2021.106475.


24. Xander M.R. Wijk V., Yun C., et al. A Liquid-Chromatography High-Resolution Mass Spectrometry Method for Non-FDA Approved Benzodiazepines. J Analyt Toxicol. 2018:1–5. Doi: 10.1093/jat/bky092.


25. Kimani M., Lanzarotta A., Batson J. Rapid determination of eight benzodiazepines in suspected counterfeit pharmaceuticals using surface-enhanced Raman scattering with handheld Raman spectrometers. J Foren Sci. 2021;66(6):2167–79. Doi: 10.1111/1556-4029.14797.


26. Frey K.A., Koeppe R.A., Holthoff V.A. In Vivo Imaging of Benzodiazepine Receptors with Positron Emission Tomography. In book: SITES of DRUG ACTION in the HUMAN BRAIN. CRC Press. 2020. Р. 29–47. Doi: 10.1201/9780367811419-3.


27. Weinstein E.A., Liu L., Ordonez A.A., et al. Noninvasive determination of 2-


28. Uddin M.N., Samanidou V.F., Papadoyannis I.N. An Overview on Total Analytical Methods for the Detection of 1,4-Benzodiazepines. Pharm Anal Acta. 2014;5:303. Doi: 10.4172/2153-2435.1000303.


29. Qriouet Z., Qmichou Z., Bouchoutrouch N., et al. Analytical Methods Used for the Detection and Quantification of Benzodiazepines. J Analyt Methods Chem. 2019;2019:11. Doi: 10.1155/2019/2035492.


30. Albishri H.M., Aldawsari N.A., Abd El-Hady D.A. Simple and Reliable Liquid Chromatographic Method for Simultaneous Determination of Five Benzodiazepine Drugs in Human Plasma. Analytica. 2022;3:251–65. Doi: 10.3390/ analytica3020018.


31. Lotfi S., Veisi H. Electrochemical determination of clonazepam drug based on glassy carbon electrode modified with Fe3O4/R-SH/Pd nanocomposite. Mater. Sci Eng C Mater Biol Appl. 2019;103:109754. Doi: 10.1016/j.msec.2019.109754.


32. Kerrigan S., Mellon M.B., Hinners P. Detection of phenazepam in impaired driving. J Analyt Toxicol. 2013;37:605–10. Doi: 10.1093/jat/bkt07.


33. Chaouali N., Moslah B., Salem K.B., et al. Illicit substances identified in the urine of 11.170 suspected drug users in North Tunisia. Pan Afr Med J. 2021;38:20. Doi: 10.11604/pamj.2021.38.20.26781.


34. Santhosh S.R., Sampath S., Gupta A. Simultaneous analysis of eight benzodiazepines in blood and urine matrix by gas chromatography-mass spectrometry: Implications for air crash investigation. Indian J Aerosp Med. 2019;63(1):2–7.


35. Nakamura M. Analyses of benzodiazepines and their metabolites in various biological matrices by LC‐MS(/MS). Biomed Chromatogr. 2011;25:1283–307. Doi: 10.1002/bmc.1598.


36. Inoue K., Ozawa Y., Toyooka T. Application of Liquid Chromatography Coupled with Electrospray Ionization Tandem Mass Spectrometry for Therapeutic Drug Monitoring of Sedative Medicine in Clinical Stage. Chromatography. 2015;36:81–92.


37. Bertol E., Vaiano F., Furlanetto S., Mari F. Cross-reactivities and structure-reactivity relationships of six benzodiazepines to EMIT immunoassay. J Pharmaceut Biomed Anal. 2013;84:168–72.


38. Feng S., Hess P.R., Wang P., et al. Chapter 13.1 – False-negative results in urine benzodiazepine immunoassay screening. Toxicology Cases for the Clinical and Forensic Laboratory. 2020. Р. 219–21. Doi: 10.1016/B978-0-12-815846-3.00051-X.


39. Mina A., McNeice L., Banukumar S., Vazquez S. Optimisation of Benzodiazepine Immunoassay Using β-Glucuronidase Enzymatic Hydrolysis: A Comparison of Five Different β-Glucuronidase Enzymes. J Biosci Med. 2022;10:7–15. doi: 10.4236/jbm.2022.101002.


40. Mina A. Comparison of several immunoassays used in drugs of abuse screening: Assessment against gold standard methods and calculation of measurement uncertainty. J Pharmacol Toxicol Methods. 2020;101:106649. Doi: 10.1016/j.vascn.2019.106649.


41. Banaszkiewicz L., Woяniak M.K., Kata M., et al. Rapid and simple multi-analyte LC–MS/MS method for the determination of benzodiazepines and Z-hypnotic drugs in blood samples: Development, validation and application based on three years of toxicological analyses. J Pharm Biomed Anal. 2020;191:113569. Doi: 10.1016/j.jpba.2020.113569.


42. Мирошниченко И.И. Мониторинг эффективности антипсихотической терапии. Психиатрия. 2022;20(4):128–38.


43. Garcia L., Tiscione N.B., Yeatman D.T., Richards-Waugh L. Novel and Nonroutine Benzodiazepines and Suvorexant by LC-MS-MS. J Anal Toxicol. 2021;45(5):462–74. Doi: 10.1093/jat/bkaa109.


Об авторах / Для корреспонденции


Автор для связи: Игорь Иванович Мирошниченко, д.м.н., зав. лаборатории фармакокинетики, Научный центр психического здоровья, Москва, Россия; igormir@psychiatry.ru 


ORCID / SPIN-код:
И.И. Мирошниченко (I.I. Miroshnichenko), https://orcid.org/0000-0003-4950-5336; SPIN-код: 4117-9703
И.И. Кузьмин (I.I. Kuzmin), https://orcid.org/0000-0002-9326-4683; SPIN-код: 1442-0325
О.Ю. Кравцова (O.Yu. Kravtsova), https://orcid.org/0000-0002-0693-2007; SPIN-код: 1733-2330
А.И. Платова (A.I. Platova), https://orcid.org/0000-0002-9682-4623; SPIN-код: 6656-2194


Похожие статьи


Бионика Медиа