SEÇİCİ SEROTONİN GERİ ALIM İNHİBİTÖRLERİNİN TABLET FORMÜLASYONLARINDA EŞ ZAMANLI TAYİNİ İÇİN RPLC YÖNTEM GELİŞTİRİLMESİ VE VALİDASYONU

Year 2023, Volume: 47 Issue: 2, 383 - 393, 20.05.2023

Ebru Çubuk Demiralay , Fatma Ürer , Zehra Üstün , Yaşar Doğan Daldal

https://doi.org/10.33483/jfpau.1199157

Abstract

Amaç: Seçici serotonin geri alım inhibitörleri (SSRI) depresyon tedavisinde en çok kullanılan bileşiklerdir. Bu bileşiklerin kromatografik ayrımları ve kantitatif tayinlerinin belirlenmesi, bileşiklerin klinik kullanımlarında ve yapılan biyofarmasötik çalışmaların başarısında oldukça önemlidir. Bu nedenle bu çalışmada tablet formülasyonunda SSRI'ların kantitatif tayini için kromatografik koşulların Ters faz sıvı kromatografi yöntemi ile optimize edilmesi amaçlanmıştır.
Gereç ve Yöntem: Çalışılan bileşikler için optimum ayırma koşulu, bileşiklerin alıkonma değerleri ile pH ve mobil faz bileşimi arasındaki ilişkiye göre belirlenmiştir. Kromatografik ayrım, hibrit bazlı ve bazik bileşiklerin tayini için yaygın olarak kullanılan X Terra C18 kolonu (250 x 4.6 mm I.D., 5 μm) kullanılarak gerçekleştirilmiştir. Geliştirilen yöntemin validasyonu; doğrusallık, kesinlik ve doğruluk parametrelerine göre yapılmıştır.
Sonuç ve Tartışma: Tablet formülasyonlarındaki etken maddelerin tayini için geliştirilen yöntem başarıyla uygulanmış ve valide edilmiştir. Elde edilen deneysel SSRI miktarları, ticari formülasyonlarda belirtilen miktarlar ile uyumlu olarak bulunmuştur. Hesaplanan geri kazanım yüzdeleri, çalışılan bileşiklerin kantitatif tayini için geliştirilen numune hazırlama tekniklerinin dış etkenlerden etkilenmediğini göstermektedir. Elde edilen sonuçlar değerlendirildiğinde, geliştirilen yöntemin çalışılan bileşiklerin rutin analizlerine uygun olduğu görülmüştür.

Keywords

Antidepresan, kantitatif analiz, metot optimizasyonu, RPLC

RPLC METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS DETERMINATION OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN TABLET FORMULATIONS

Abstract

Objective: Selective serotonin reuptake inhibitor (SSRIs) compounds are the most used compounds in the treatment of depression. The determination of chromatographic separation and quantitative determination of these compounds is very important in the clinical use of these compounds and the success of biopharmaceutical studies. For this reason, this study, it was aimed to optimize the chromatographic conditions for the quantitative determination of SSRIs in tablet formulation by Reversed phase liquid chromatography method.
Material and Method: The optimum separation condition for the studied compounds was determined based on the relationship between the retention values of the compounds and the pH and the content of the mobile phase. Chromatographic determination was made on the X Terra C18 column (250 x 4.6 mm I.D., 5 μm), which is widely used for the determination of hybrid-based and basic compounds. The validation of the developed method was carried out based on the parameters of linearity, precision, and accuracy.
Result and Discussion: The developed and validated method was successfully applied for the determination of active ingredients in the tablet dosage form. The experimental results of the amount of studied SSRIs in selected commercial tablets are in good agreement with the label claims. The calculated percent recoveries show that the sample preparation techniques developed for the quantification of the compounds studied are not affected by interferences. The evaluation of the obtained results showed that the developed method is suitable for the routine use of studied compounds.

Keywords

Antidepressant, method optimization, quantitative analysis, RPLC

References

• 1. Jacobsen, N.W., Hansen, C.H., Nellemann, C., Styrishave, B., Halling-Sørensen, B. (2015). Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicology in Vitro, 29, 1729-1735. [CrossRef]
• 2. Bermel, R.A., Hashmonay, R., Meng, X., Randhawa, S., Von Rosenstiel, P., Sfikas, N., Kantor, D. (2015). Fingolimod first-dose effects in patients with relapsing multiple sclerosis concomitantly receiving selective serotonin-reuptake inhibitors. Multiple Sclerosis and Related Disorders, 4, 273-280. [CrossRef]
• 3. Aronson, J.K. (2016). Meyler’s Side Effects of Drugs (16. edition). Netherlands, Elsevier.
• 4. Hoirisch-Clapauch, S., Nardi, A.E., Gris, J.C., Brenner, B. (2014). Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects? Thrombosis Research, 134(1), 11-16. [CrossRef]
• 5. Chemicalize program. http://www.chemicalize.org (accessed 29 October 2022).
• 6. Şentürk, Z., Saka, C., Teğin, İ. (2011). Analytical methods for determination of selective serotonin reuptake inhibitor antidepressants. Reviews in Analytical Chemistry, 30(2), 87-122. [CrossRef]
• 7. Murtada, K., de Andrés, F., Ríos, A., Zougagh, M. (2018). Determination of antidepressants in human urine extracted by magnetic multiwalled carbon nanotube poly (styrene‐co‐divinylbenzene) composites and separation by capillary electrophoresis. Electrophoresis, 39(14), 1808-1815. [CrossRef]
• 8. Annapurna, V., Jyothi, G., Nagalakshmi, V., Sailaja, B.B.V. (2010). Spectrophotometric methods for the assay of fluvoxamine using chromogenic reagents. E-Journal of Chemistry, 7(4), 1539-1545. [CrossRef]
• 9. Kazakevich, Y., Lobrutto, R. (2007). HPLC for Pharmaceutical Scientists (1st edition), Wiley-Interscience, Canada, p.1140.
• 10. Meyer, V.R. (2010). Practical High-Performance Liquid Chromatography (16th edition), John Wiley and Sons, United Kingdom, p.432.
• 11. Daldal, Y.D., Demiralay, E.Ç., Ozkan, S.A. (2016). Effect of organic solvent composition on dissociation constants of some reversible acetylcholinesterase inhibitors. Journal of the Brazilian Chemical Society, 27, 493-499. [CrossRef]
• 12. Daldal, Y.D., Demiralay, E.Ç. (2020). Chromatographic and UV-visible spectrophotometric pKa determination of some purine antimetabolites. Journal of Molecular Liquids, 317, 113930. [CrossRef]
• 13. Guideline, I.H.T. (2005). Validation of analytical procedures: Text and methodology. Q2 (R1), 1(20), 05.
• 14. Demiralay, E.Ç., Koç, D., Daldal, Y.D., Çakır, C. (2012). Determination of chromatographic and spectrophotometric dissociation constants of some beta lactam antibiotics. Journal of Pharmaceutical and Biomedical Analysis, 71, 139-143. [CrossRef]
• 15. Demiralay, E.Ç., Üstün, Z., Daldal, Y.D. (2014). Estimation of thermodynamic acidity constants of some penicillinase-resistant penicillins. Journal of Pharmaceutical and Biomedical Analysis, 91, 7-11. [CrossRef]
• 16. Demiralay, E.Ç. (2012). An experimental design approach to optimization of the liquid chromatographic separation conditions for the determination of metformin and glibenclamide in pharmaceutical formulation. Acta Chimica Slovenica, 59(2), 307-314.
• 17. Lundstedt, T., Seifert, E., Abramo, L., Thelin, B., Nyström, Å., Pettersen, J., Bergman, R. (1998). Experimental design and optimization. Chemometrics and intelligent laboratory systems, 42(1-2), 3-40. [CrossRef]
• 18. Bolton, S., Bor, S. (2003). Pharmaceutical Statistics: Practical and Clinical Applications, Revised and Expanded (4th edition), CRC press, Boca Raton, p.755.
• 19. Bonazzi, D., Gotti, R., Andrisano, V., Cavrini, V. (1997). Analysis of ACE inhibitors in pharmaceutical dosage forms by derivative UV spectroscopy and liquid chromatography (HPLC). Journal of Pharmaceutical and Biomedical Analysis, 16(3), 431-438. [CrossRef]
• 20. Grover, P., Bhardwaj, M., Mukherjee, D. (2022). Identification and characterization of forced degradation products of sertraline hydrochloride using UPLC, ultra-high-performance liquid Chromatography-Quadrupole-Time of flight mass spectrometry (UHPLC-Q-TOF/MS/MS) and NMR. Journal of Pharmaceutical and Biomedical Analysis, 221, 115045. [CrossRef]
• 21. Ghane, M., Mohadesi, A., Ezoddin, M., Ali Karimi, M., Abdi, K. (2022). Dispersive liquid–liquid microextraction with back extraction based on in situ deep eutectic solvent decomposition and air-assisted for determination of some antidepressant drugs in biological samples prior to HPLC-UV. International Journal of Environmental Analytical Chemistry, 1-15. [CrossRef]
• 22. Kovatsi, L., Manousi, N., Papadoyannis, I. (2016). Direct UHPLC-DAD Method to Determine Asenapine, Paroxetine and Fluvoxamine in Human Blood Serum, Urine and Cerebrospinal Fluid. Current Pharmaceutical Analysis, 12(4), 349-356.
• 23. Fernández, P., Taboada, V., Regenjo, M., Morales, L., Alvarez, I., Carro, A.M., Lorenzo, R. (2016). Optimization of ultrasound assisted dispersive liquid-liquid microextraction of six antidepressants in human plasma using experimental design. Journal of Pharmaceutical and Biomedical Analysis, 124, 189-197. [CrossRef]
• 24. Budău, M., Hancu, G., Muntean, D.L., Papp, L.A., Cârje, A.G., Garaj, V. (2020). Enantioseparation of citalopram enantiomers by capillary electrophoresis: Method development through experimental design and computational modeling. Chirality, 32(8), 1119-1128. [CrossRef]
• 25. Abdel‐Raoof, A.M., Hasan, M.A., Madkour, A.W., Abdel‐Fattah, A., Eissa, M.S. (2021). Simultaneous determination of citalopram and tadalafil by the second derivative synchronous fluorescence method in biological fluids; application of Box-Behnken optimization design. Luminescence, 36(1), 57-65. [CrossRef]
• 26. Yılmaz, H., Üstün, Z., Demiralay, E.Ç. (2016). RPLC determination of acid dissociation constants and quantitative estimation for sulfasalazine. Journal of the Iranian Chemical Society, 13, 103-110. [CrossRef]
• 27. Yılmaz, H., Demiralay, E.Ç. (2015). Investigation of chromatographic behavior of leflunomide and its identification in pharmaceutical dosage form by reversed phase liquid chromatography. Journal of Liquid Chromatography & Related Technologies, 38(1), 97-103. [CrossRef]
• 28. Miguel, L., Barbas, C. (2003). LC determination of impurities in azithromycin tablets. Journal of Pharmaceutical and Biomedical Analysis, 33(2), 211-217. [CrossRef]
• 29. Volná, T., Motyka, K., Hlaváč, J. (2017). RP-HPLC determination of dissociation constant using solely aqueous mobile phase. Journal of Pharmaceutical and Biomedical Analysis, 134, 143-148. [CrossRef]
• 30. Barbosa, J., Bergés, R., Sanz-Nebot, V., Toro, I. (1999). Chromatographic behavior of ionizable compounds in liquid chromatography. Part 2. Standardization of potentiometric sensors and effect of pH and ionic strength on the retention of analytes using acetonitrile-water mobile phases. Analytica Chimica Acta, 389(1-3), 43-52. [CrossRef]
• 31. Agrafiotou, P., Ràfols, C., Castells, C., Bosch, E., Rosés, M. (2011). Simultaneous effect of pH, temperature and mobile phase composition in the chromatographic retention of ionizable compounds. Journal of Chromatography A, 1218(30), 4995-5009. [CrossRef]
• 32. Vonaparti, A., Kazanis, M., Panderi, I. (2006). Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the determination of benazepril, benazeprilat and hydrochlorothiazide in human plasma. Journal of Mass Spectrometry, 41(5), 593-605. [CrossRef]
• 33. Paszun, S.K., Stanisz, B., Pawłowski, W. (2012). Rapid and simple stability indicating HPLC method for the determination of cilazapril in pure substance and pharmaceutical formulation in comparison with classic and derivative spectrophotometric methods. Acta Poloniae Pharmaceutica, 69(2), 193-201.
• 34. Swartz, M.E., Krull, I.S. (2012). Handbook of analytical validation (1st edition), CRC Press, Boca Raton, p.220.