Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 24, Art. 52 (pp. 701-714)    |    2023       

»

Development and validation of a methodology for quantitative determination of escitalopram in human blood plasma by hplc-ms/ms for pharmacokinetics and drug monitoring tasks

Vasilyuk V.B.1,2, Sinyavin S.A.1, Fomichev A.V.1, Verveda A.B.1,3, Faraponova М.V 1

1Limited Liability Company «Research Center Eco-Safety»
2North-Western State Medical University named after I.I. Mechnikov
3Research Institute of Industrial and Maritime Medicine of Federal Medical Biological Agency

Brief summary

The issues of quantitative determination of escitalopram in biological media, as the most common drug from the group of antidepressants, are relevant for psychiatry, toxicology, forensic medicine, clinical pharmacology and research activities. Objective. Development and validation of a technique for rapid quantitative determination of escitalopram in human blood plasma for the purposes of clinical medicine and research activities. Materials and Methods. Equipment: HPLC-MS/MS system consisting of a liquid chromatograph Agilent 1260 Infinity II with tandem mass-selective detector G6470B (triple quadrupole, Agilent Technologies, USA) with software MassHunter (Ver. 10.1). Reagents and solutions: acetonitrile (LC-MS grade, Merck, Germany); methanol (HPLC-grade, Химмед, Russia); formic acid (Химмед, Russia), standard samples of escitalopram oxalate (CAS 128196-01-0, Synergene Active Ingredience Pvt. Ltd, India) and paroxetine hydrochloride (CAS 61869-08-7, TRC Canada, Canada). Results. A method of quantitative determination of escitalopram has been developed, which has been validated in accordance with the rules of the Eurasian Economic Union, as well as the requirements of the guidelines of FDA and ЕМА. Conclusion. As part of the study, a method for the quantitative determination of escitalopram in blood plasma was developed and validated. The analytical range of the technique is 0.5 - 100.0 ng/ml. The advantage of the developed methodology is the simplicity of execution and the speed of analytical research (about 20 minutes).


Key words

escitalopram; liquid chromatography-mass spectrometry; chromatography; mass spectrometry; pharmacokinetics; bioanalytical technique.

Reference list

1. Klinicheskie rekomendacii. «Depressivnii epizod, Rekyrrentnoe depressivnoe rasstroistvo» 2021 Rossiiskoe Obshestvo Psihiatrov


2. Keller M.B. Citalopram therapy for depression: a review of 10 years of European experience and data from US clinical trials. Journal ofClin. Psychiatry. 2000; 61:896-908. PMID: 11206593


3. Grover S., Avasth A., Kalita K. et al. IPS multicentric study: Antidepressant prescription patterns. Indian journal of psychiatry. 2013;55(1), 41.doi: 10.4103/0019-5545.105503


4. Stahl S.M., Gergel I., Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Journal ofClin Psychiatry. 2003; 64 (11): 1322-7. doi: 10.4088/jcp.v64n1107


5. Klinicheskie rekomendacii «Otravlenie psihotropnimi sredstvami, ne klassificirovannoe v drygih rybrikah (T43)», 2020


6. Illarionova E.A. Sydebno-himicheskoe otdelenie Buro sydebno-medicinskoi ekspertizi: ychebnoe posobie. FGBOY VO IGMY Minzdrava Rossii, Kafedra farmacevticheskoi i toksikologicheskoi himii. - Irkytsk: IGMY, 2020.


7. Drewes P., Tjijssen I., Mengel H., Larsen F. A single dose cross-over pharmacokinetic study comparing racemic citalopram (40 mg) with the S-enantiomer of citalopram (escitalopram, 20 mg) in healthy male subjects. 41st Annual Meeting of the New Clinical Drug Evaluation Unit, Phoenix, AZ, USA (28-31 May 2001).


8. Joffe P., Larsen F.S., Pedersen V. et al. Single dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects. Eur J ClinPharmacol. 1998; 54 (3): 237-42.doi:10.1007/s002280050452


9. Klinicheskaya psihofarmakogenetika pod red. R.F. Nasirovoi, N.G. Neznanova. SPb: Izdatelstvo DEAN, 2019.


10. Sogaard B., Mengel H., Rao N. et al. The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. J ClinPharmacol. 2005; 45 (12): 1400-6.doi: 10.1177/0091270005280860


11. Klein N., Sacher J., Geiss-Granadia T., et al. Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I] ADAM SPECT study. Psychopharmacology (Berl) 2007;191(2):333-9. doi:10.1007/s00213-006-0666-y


12. Waugh J., Goa K.L. Escitalopram: a review of its use in the management of major depressive and anxiety disorders. CNS Drugs. 2003;17(5):343-362. doi: 10.2165/00023210-200317050-00004


13. Von Moltke L.L., Greenblatt D.J., Giancarlo G.M. et al. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug MetabDispos. 2001;29(8):1102-9. PMID: 11454728


14. Sidhu J., Priskorn M., Poulsen M. et al. Steady state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans. Chirality 1997; 9(7): 686- 92. doi:10.1002/(SICI)1520-636X(1997)9:73.0.CO;2-5


15. Rochat B., Kosel M., Boss G. et al. Stereoselective biotransformation of the selective serotonin reuptake inhibitor citalopram and its demethylated metabolites by monoamine oxidases in human liver. Biochemical Pharmacology. 1998; 56 (1): 15-23.doi:10.1016/s0006-2952(98)00008-2


16. Gutierrez M., Mengel H. Pharmacokinetics of escitalopram. 42nd Annual New Clinical Drug Evaluation Unit (NCDEU) Meeting, Boca Raton, FL, USA (10-13 June 2002).


17. Spigset O., Ha¨gg S., Stegmayr B. et al. Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis. Eur J Clin Pharmacology. 2000;56(9-10):699-703.doi:10.1007/s002280000205


18. Kaushik KH, Vijay Kumar S, Nagulu M. Narasimha Pharmacokinetics and Bioavailability Comparison of two oral Tablet Formulations of Escitalopram 20 mg: A Single-Dose, Open-Label, Two-Period Crossover Study in Healthy Indian Adult Subjects. Iranian Journal of Pharmaceutical Sciences. 2014, 10(1):69-82. DOI 10.1321/bcpt.13132.


19. Canbolat, Fadime; Erinç, Dilek Meltem Tasdemir; Evrensel, Alper; Aydın, Ahmet; Tarhan, Kaşif Nevzat/ Quantitation of escitalopram and its metabolites by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) in psychiatric patients: New metabolic ratio establishmet. Basic&Clinical Pharmacology&Toxicology. 2018, 26(4):491-6. DOI 10.1111/bcpt.13133.


20. PRILOJENIE 6 k Pravilam provedeniya issledovanii bioekvivalentnosti lekarstvennih preparatov v ramkah Evraziiskogo ekonomicheskogo souza (ytverjdeni resheniem ?85 Soveta Evraziiskoi ekonomicheskoi komissii ot 03.11.2016 g.).


21. Guidance for Industry: Bioanalytical method validation. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evolution and Research (CDER). U.S. Government Printing Office: Washington, DC, 2018.


22. Guideline on bioanalytical method validation. European Medicines Agency. Committee for medicinal products for human use: London, 2011.