Merkezi Kompozit Dizayn Kullanılarak Kapesitabin Tayini için RPLC Yönteminin Geliştirilmesi ve Validasyonu

Year 2020, Volume: 24 Issue: 1, 105 - 112, 20.04.2020

Yaşar Doğan Daldal , Ebru Çubuk Demiralay

https://doi.org/10.19113/sdufenbed.582980

Cited By: 2

Abstract

Ters faz sıvı kromatografi (RPLC) yöntemi, merkezi kompozit dizayn (CCD) kullanılarak kapesitabinin analizi için geliştirilmiş ve valide edilmiştir. Metot üç faktörle (mobil faz organik modifiyer derişimi, mobil faz pH’sı ve kolon sıcaklığı) Minitab programı kullanılarak optimize edilmiştir. Optimum kromatografik koşullar, Derringer’in istenebilirlik fonksiyonu kullanılarak belirlenmiştir. CCD'nin yardımıyla tayin edilen ayırmanın optimum koşulları: (1) Mobil faz: asetonitril-su ikili karışımı oranı 40:60 (%h/h), (2) kolon sıcaklığı 32oC ve mobil fazın pH'sı 7,5'dur. Çalışma, YMC triart C18 (150x4,6 mm I.D, 3m) kolonda ve 1 mL/dakika akış hızında gerçekleştirilmiştir. Geliştirilen sıvı kromatografik yöntemin ICH parametrelerine göre validasyonu gerçekleştirilmiştir.

Keywords

Kapesitabin, Rivastigmin, Merkezi kompozit dizayn, Metot validasyonu

Supporting Institution

Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi Başkanlığı

Project Number

4581-D2-16

Thanks

Bu çalışma Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi Başkanlığı 4581-D2-16 nolu proje ile desteklenmiştir. Çalışmamızı maddi olarak destekleyen Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi Başkanlığına teşekkür ederiz.

Development and Validation of a RPLC Method for the Determination of Capecitabine using Central Composite Design

Abstract

A reversed phase liquid chromatographic (RPLC) method was developed and validated for analysis of capecitabine using central composite design (CCD).The method was optimized using Minitab software with three factors (mobile phase organic modifier concentration, pH of the mobile phase and column temperature). The optimum chromatographic conditions were determined using Derringer's desirability function. The optimum conditions of separation (optimum values of significant factors) determined with the aid of CCD were: (1) mobile phase: The acetonitrile:water binary mixture ratio is 40:60 (%, v/v), (2) column temperature 32oC and (3) pH of the mobile phase is 7.5. The study was carried out on a YMC triart C18(150x4.6 mm I.D, 3m) column and at a flow rate of 1 mL/min.The validation of the developed liquid chromatographic method according to ICH parameters was performed.

Keywords

Capecitabine, Rivastigmine, Central composite design, Method validation

Project Number

4581-D2-16

References

• [1] Tozkoparan, B., Aytaç, S.P., 2007. Kanser kemoterapisinde terapötik hedef olarak glutatyon s-transferazlar. Hacettepe Üniversitesi, Eczacılık Fakültesi Dergisi, 27(2), 139-64.
• [2] Domaç, M. (Ed.) 2005. Kemoterapötikler. Fersa Matbaacılık Ltd., Ankara,96s.
• [3] Kayaalp, O. 2000. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. Hacettepe-Taş Kitapçılık Ltd. Şti, Ankara, 880s.
• [4] Süzer, Ö. (Ed.) 2009. Goodman & Gillman Tedavinin Farmakolojik Temeli. Nobel Tıp Kitabevi, Ankara, 2017s.
• [5] Kazakevich, Y., Lobrutto, Y. 2007. HPLC for Pharmaceutical Scientists. Wiley-Interscience, Canada, USA, 1135s.
• [6] ICH Expert Working Group, 2005, April. Validation of analytical procedures: text and methodology Q2 (R1). In Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland.
• [7] Meyer, V.R. 2010. Practical High-Performance Liquid Chromatography. John Wiley and Sons, Ltd., United Kingdom, 428s.
• [8] Uysal, R., Daldal, Y.D., Üstün, Z., Çubuk Demiralay, E. 2017. Optimization of RPLC Method for Separation of Some Acetylcholinesterase Inhibitors by using Central Composite Design. Eurasian Journal of Analytical Chemistry, 12(1), 23-43.
• [9] Gündoğan, B., Çubuk Demiralay, E., Daldal, Y.D., Üstün, Z. 2017. Determination of Optimum Separation Condition for Some Carbapenem Antibiotics Using RPLC with the Aid of Central Composite Design and Desirability Function. Current Pharmaceutical Analysis, 13,100-109.
• [10] Çubuk Demiralay, E. 2012. An Experimental Design Ap proach to Optimization of the Liquid Chromatographic Separation Conditions for the Determination of Metformin and Glibenclamide in Pharmaceutical Formulation. Acta Chima Slovenica, 59(2), 307-314.
• [11] Myers, R.H., Montgomery, D.C. 2002. Response Surface Methodology. Wiley, New York, 798s.
• [12] Montgomery, D.C. 2005. Design and Analysis of Experiments. John Wiley &Sons, Westford, 757s.
• [13] Meloun, M., Zuzana Ferenčiková, Vrána, A. 2011. Determination of The Thermodynamic Dissociation Constant of Capecitabine Using Spectrophotometric and Potentiometric Titration Data.The Journal of Chemical Thermodynamics, 43, 930–937.
• [14] Ɫaszcz,M., Trzcińska, K., Filip, K., Szyprowska, A., Mucha, M., Krzeczyński, P. 2011. Stability Studies of Capecitabine. Journal of Thermal Analysis and Calorimetry, 105, 1015-1021.
• [15] Pujeri, S.S., Khader, A. M. A., Seetharamappa, J. 2012. Stability Study of CapecitabineActive Pharmaceutical Ingredient in Bulk Drug and PharmaceuticalFormulation. Journal of Liquid Chromatography & Related Technologies, 35, 40-49.
• [16] Wang, X.J, You, J.Z. 2016. Study on The Thermal Decomposition of Capecitabine. Journal of Thermal Analysis and Calorimetry, 123, 2485-2497.
• [17] Farkouh, A., Ettlinger, D., Schueller, J., Georgopoulos, A., Scheithauer, W., Czejka, M. 2010. A Rapid and Simple HPLC Assay for Quantification ofCapecitabine for Drug Monitoring Purposes. Anticancer Research,30, 5207-5212.
• [18] Deenen, M.J., Rosing, H., Hillebrand, M.J., Schellens, J.H.M., Beijnen, J. H. 2013. Quantitative Determination of Capecitabine and İts Six Metabolites in HumanPlasma Using Liquid Chromatography Coupled to Electrospray Tandem MassSpectrometry. Journal of Chromatography B, 913, 30– 40.
• [19] Deng, P., Ji, C., Daia, X., Zhong, D., Ding, L., Chen, X. 2015. Simultaneous Determination of Capecitabine and its Three Nucleosidemetabolites in Human Plasma by High Performance Liquid Chromatography-Tandem Mass Spectrometry. Journal of Chromatography B, 989, 71–79.
• [20] Jacobs, B. A.W., Rosing, H., de Vries, N., Meulendijks, D., Henricks, L. M., Schellens, J.H.M., Beijnen, J.H. 2016. Development and Validation Of A Rapid and Sensitive UPLC–MS/MS Method for Determination of Uracil and Dihydrouracil in Human Plasma. Journal of Pharmaceutical and Biomedical Analysis, 126, 75-82.
• [21] Stashkevich, M.A., Khomutov, E.V., Dumanskii, Y.V.,Matvienko, A.G., Zinkovich, I.I. 2016. Effect of 5-Fluorouracil on Thymidine Phosphorylasectivity in Model Experiment. Bulletin of Experimental Biology and Medicine, 160(5),646-647.
• [22] Daldal, Y.D. 2018. Kemoterapide kullanılan bazı antimetabolit ilaçların sıvı kromatografik tayininde merkezi kompozit dizayn tekniğinin uygulanması. Süleyman Demirel Üniversitesi, Fen Bilimleri Enstitüsü, Doktora Tezi, 233s, Isparta.
• [23] 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(3), 493-499.