phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.37489/2587-7836-2022-4-26-32phkinetica-340Research ArticleМЕТОДЫ ОПРЕДЕЛЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВDRUGS DETERMINATION METHODSКоличественное определение содержания венлафаксина и его активного метаболита в плазме крови человека посредством хроматомасс-спектрометрииQuantitative determination of the content of venlafaxine and its active metabolite in human plasma using liquid chromatography-mass spectrometryhttps://orcid.org/0000-0002-9326-4683КузьминИ. И.KuzminI. I.

Кузьмин Иван Игоревич, м. н. с. лаборатории доказательной медицины и биостатистика

Москва

Kuzmin Ivan I., Research assistant of laboratory of evidence-based medicine and biostatistics

SPIN code: 1442-0325

Moscow

rouswell9@gmail.comhttps://orcid.org/0000-0002-9682-4623ПлатоваА. И.PlatovaA. I.

Платова Ангелина Игоревна, м. н. с. лаборатории фармакокинетики

Москва

Platova Angelina I., Research assistant of pharmacokinetics laboratory

SPIN code: 6656-2194

Moscow

platova@psychiatry.ruhttps://orcid.org/0000-0001-5216-5294КонстантиноваА. С.KonstantinovaA. S.

Константинова Анастасия Сергеевна, Сервис-инженер

Москва

Konstantinova Anastasiya S., Service Engineer

Moscow

https://orcid.org/0000-0003-4950-5336МирошниченкоИ. И.MiroshnichenkoI. I.

Мирошниченко Игорь Иванович, д. м. н., заведующий лабораторией фармакокинетики

Москва

Miroshnichenko Igor I., Dr. Sci. (Med.), Head of pharmacokinetics laboratory

SPIN code: 4117-9703

Moscow

igormir@psychiatry.ruФГБНУ «Научный центр психического здоровья»РоссияFSBSI «Mental Health Research Center»Russian FederationООО «ЛАБИНВЕСТ»РоссияLABINVEST LLCRussian Federation202218012023042632Copyright © Кузьмин И.И., Платова А.И., Константинова А.С., Мирошниченко И.И., 20232023Кузьмин И.И., Платова А.И., Константинова А.С., Мирошниченко И.И.Kuzmin I.I., Platova A.I., Konstantinova A.S., Miroshnichenko I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/340

Предложен валидированный метод количественного определения венлафаксина и О-десметилвенлафаксина в плазме крови человека посредством жидкостной тандемной хроматомасс-спектрометрии (ВЭЖХ-МС/MC). Пробоподготовку проводили жидкофазной экстракцией с поддержкой (SLE, от англ. «supported liquid extraction») с использованием картриджей HyperSEP и промывкой 3-метилбутиловым эфиром. Для измерения содержания целевых веществ использовали тройной квадрупольный масс-спектрометр в режиме детектирования заданных масс (+MRM) в условиях ионизации электрораспылением. Калибровочные кривые носили линейный характер (коэффициент достоверности аппроксимации r2 > 0,999). Валидация метода свидетельствовала о достаточно высокой чувствительности, специфичности, правильности и воспроизводимости, а также стабильности аналитов при замораживании–оттаивании и хранении при температуре –20 °С. Метод разработан для применения в терапевтическом лекарственном мониторинге (ТЛМ).

A validated method for the quantitative determination of venlafaxine, O-desmethylvenlafaxine in human plasma by tandem liquid chromatographymass spectrometry (HPLC/MS/MS) has been proposed. Sample preparation was carried out by liquid-phase extraction with support (SLE, from «supported liquid extraction») using HyperSEP cartridges and washing with 3-methylbutyl ether. The measure of the target analytes was carried on a triple quadrupole mass spectrometer under multiple-reaction monitoring (+MRM) mode with the electrospray ionization. The calibration curves were linear with regression coefficient r2 > 0.999. The method validation was showed high sensitivity, specificity, accuracy and reproducibility, as well as stability of analytes after freeze/thaw cycles and storage at –20 °C. The method is developed for using in therapeutic drug monitoring.

венлафаксино-десметилвенлафаксинхроматомасс-спектрометрияжидкофазная экстракция с поддержкойvenlafaxineO-desmethylvenlafaxinechromatomass spectrometrysupport liquid phase extractionReferencesYuan Z, Chen Z, Xue M, Zhang J, Leng L. Application of antidepressants in depression: A systematic review and meta-analysis. J Clin Neurosci. 2020;80:169–181. DOI: 10.1016/j.jocn.2020.08.013.Yuan Z, Chen Z, Xue M, Zhang J, Leng L. Application of antidepressants in depression: A systematic review and meta-analysis. J Clin Neurosci. 2020;80:169–181. DOI: 10.1016/j.jocn.2020.08.013.Sánchez-Mata MC, Cámara-Hurtado M, Díez-Marqués C, Torija-Isasa ME. Comparison of high-performance liquid chromatography and spectrofluorimetry for vitamin C analysis of green beans (Phaseolus vulgaris L.). Eur Food Res Technol. 2000;210(3):220–225. DOI: 10.1007/PL00005516.Sánchez-Mata MC, Cámara-Hurtado M, Díez-Marqués C, Torija-Isasa ME. Comparison of high-performance liquid chromatography and spectrofluorimetry for vitamin C analysis of green beans (Phaseolus vulgaris L.). Eur Food Res Technol. 2000;210(3):220–225. DOI: 10.1007/PL00005516.Shelton RC. Serotonin and Norepinephrine Reuptake Inhibitors. Handb Exp Pharmacol. 2019;250:145–180. DOI: 10.1007/164_2018_164.Shelton RC. Serotonin and Norepinephrine Reuptake Inhibitors. Handb Exp Pharmacol. 2019;250:145–180. DOI: 10.1007/164_2018_164.Hancu G, Lupu D, Milan A, Budău M, Barabás–Hajdu E. Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies. Biomedical Chromatograph. 2021;35(1):e4874. DOI: 10.1002/bmc.4874.Hancu G, Lupu D, Milan A, Budău M, Barabás–Hajdu E. Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies. Biomedical Chromatograph. 2021;35(1):e4874. DOI: 10.1002/bmc.4874.Мирошниченко И. И. Рациональное дозирование и мониторинг лекарственных средств // М.: Медицинское информационное агентство. М.: Мед. Информ; 2011, 416 с.Miroshnichenko II. Racional'noe dozirovanie i monitoring lekarstvennyh sredstv. Moscow: Medical News Agency. 2011. (In Russ).Ganesh SV, Beunk L, Nikolik B, van der Weide J, Bet PM. Therapeutic drug monitoring of psychotropics as a diagnostic tool for CYP2D6 poor metabolizer phenotype. Ther Drug Monit. 2021;43(5):672–680. DOI: 10.1097/FTD.0000000000000868.Ganesh SV, Beunk L, Nikolik B, van der Weide J, Bet PM. Therapeutic drug monitoring of psychotropics as a diagnostic tool for CYP2D6 poor metabolizer phenotype. Ther Drug Monit. 2021;43(5):672–680. DOI: 10.1097/FTD.0000000000000868.Scherf-Clavel M, Weber H, Wurst C, Stonawski S, Hommers L, Unterecker S, Wolf C, Domschke K, Rost N, Brückl T, Lucae S, Uhr M, Binder EB, Menke A, Deckert J. Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response. Pharmacopsychiatry. 2022;55(05):246–254. DOI: 10.1055/a-1872-0613.Scherf-Clavel M, Weber H, Wurst C, Stonawski S, Hommers L, Unterecker S, Wolf C, Domschke K, Rost N, Brückl T, Lucae S, Uhr M, Binder EB, Menke A, Deckert J. Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response. Pharmacopsychiatry. 2022;55(05):246–254. DOI: 10.1055/a-1872-0613.Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. Pharmacopsychiatry. 2018 Jan;51(1-02):9–62. DOI: 10.1055/s-0043-116492.Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. Pharmacopsychiatry. 2018 Jan;51(1-02):9–62. DOI: 10.1055/s-0043-116492.Chenu F, Batten LA, Zernig G, et al. Comparison of pharmacokinetic profiles of brand-name and generic formulations of citalopram and venlafaxine: a crossover study. J Clin Psychiatry. 2009;70(7):958–966. DOI: 10.4088/jcp.09m05315.Chenu F, Batten LA, Zernig G, et al. Comparison of pharmacokinetic profiles of brand-name and generic formulations of citalopram and venlafaxine: a crossover study. J Clin Psychiatry. 2009;70(7):958–966. DOI: 10.4088/jcp.09m05315.Couchman L, Morgan PE, Spencer EP, et al. Plasma clozapine and norclozapine in patients prescribed different brands of clozapine (Clozaril, Denzapine, and Zaponex). Ther Drug Monit. 2010;32(5): 624–627. DOI: 10.1097/FTD.0b013e3181f0a1a2.Couchman L, Morgan PE, Spencer EP, et al. Plasma clozapine and norclozapine in patients prescribed different brands of clozapine (Clozaril, Denzapine, and Zaponex). Ther Drug Monit. 2010;32(5): 624–627. DOI: 10.1097/FTD.0b013e3181f0a1a2.Сервие К.Ю., Апраксин В.Ф., Анисимова Н.А., Киреева А.В., Куклин В.Н. Определение препарата «Венлафаксин» в биологических жидкостях. Фармация. 2018;67(6):13–19.Servie KYu, Apraksin VF, Anisimova NA, Kireeva AV, Kuklin VN. Determination of Venlafaxine in biological fluids. Farmatsiya. 2018;67(6):13–19. (In Russ). DOI: 10.29296/25419218-2018-06-03.Truta L, Castro AL, Tarelho S, Costa P, Sales MGF, Teixeira HM. Antidepressants detection and quantification in whole blood samples by GC–MS/MS, for forensic purposes. J Pharm Biomed Anal. 2016;128:496–503. DOI: 10.1016/j.jpba.2016.06.027.Truta L, Castro AL, Tarelho S, Costa P, Sales MGF, Teixeira HM. Antidepressants detection and quantification in whole blood samples by GC–MS/MS, for forensic purposes. J Pharm Biomed Anal. 2016;128:496–503. DOI: 10.1016/j.jpba.2016.06.027.Sher M, Ahmad M, Hassan F, Naeem-ul-Hassan M, & Hussain MA. Development and validation of an HPLC-UV method for accelerated stability study and pharmacokinetic analysis of venlafaxine. Brazilian Journal of Pharmaceutical Sciences. 2020;56. DOI: 10.1590/s2175-97902019000217728.Sher M, Ahmad M, Hassan F, Naeem-ul-Hassan M, & Hussain MA. Development and validation of an HPLC-UV method for accelerated stability study and pharmacokinetic analysis of venlafaxine. Brazilian Journal of Pharmaceutical Sciences. 2020;56. DOI: 10.1590/s2175-97902019000217728.Shen S, Zhang C, Mao Y. Determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma by HPLC fluorescence. Gen Psychiatr. 2018;31(2):e000010. DOI: 10.1136/gpsych-2018-000010.Shen S, Zhang C, Mao Y. Determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma by HPLC fluorescence. Gen Psychiatr. 2018;31(2):e000010. DOI: 10.1136/gpsych-2018-000010.Bhatt J, Jangid A, Venkatesh G, Subbaiah G, & Singh S. Liquid chromatography–tandem mass spectrometry (LC–MS–MS) method for simultaneous determination of venlafaxine and its active metabolite O-desmethyl venlafaxine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;829(1-2):75–81. DOI: 10.1016/j.jchromb.2005.09.034.Bhatt J, Jangid A, Venkatesh G, Subbaiah G, & Singh S. Liquid chromatography–tandem mass spectrometry (LC–MS–MS) method for simultaneous determination of venlafaxine and its active metabolite O-desmethyl venlafaxine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;829(1-2):75–81. DOI: 10.1016/j.jchromb.2005.09.034.Zhang Y, Cao H, & Jiang H. Supported liquid extraction versus liquid–liquid extraction for sample preparation in LC–MS/MS-based bioanalysis. Bioanalysis. 2013;5(3):285–288. DOI: 10.4155/bio.12.335.Zhang Y, Cao H, & Jiang H. Supported liquid extraction versus liquid–liquid extraction for sample preparation in LC–MS/MS-based bioanalysis. Bioanalysis. 2013;5(3):285–288. DOI: 10.4155/bio.12.335.Hansen MR, Kuhlmann IB, Pottegård A, Damkier P. Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age, Sex and Dose Concentration Relationships. Basic Clin Pharmacol Toxicol. 2017;121(4):298–302. DOI: 10.1111/bcpt.12796.Hansen MR, Kuhlmann IB, Pottegård A, Damkier P. Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age, Sex and Dose Concentration Relationships. Basic Clin Pharmacol Toxicol. 2017;121(4):298–302. DOI: 10.1111/bcpt.12796.Peters FT, Drummer OH, Musshoff F. Validation of new methods. Forensic Sci Int. 2007;165(2-3):216–224. DOI: 10.1016/j.forsciint.2006.05.021.Peters FT, Drummer OH, Musshoff F. Validation of new methods. Forensic Sci Int. 2007;165(2-3):216–224. DOI: 10.1016/j.forsciint.2006.05.021.

The authors declare that there are no conflicts of interest present.