Piroksikamın pKa Değerinin Yüksek Performanslı Sıvı Kromatografisi ile Belirlenmesi

Year 2021, Issue: 32, 711 - 715, 31.12.2021

Murat Soyseven , Burcu Sezgin , Göksel Arli

https://doi.org/10.31590/ejosat.1039852

Abstract

Bu çalışmada bir nonsteroid anti-inflamatuvar ilaç olan piroksikamın ters faz sıvı kromatografi yöntemiyle farklı asetonitril-su ikili karışımlarındaki ve sudaki asidik iyonlaşma sabitleri (pKa) belirlenmiştir. Piroksikamın kromatografik davranışına hareketli fazın pH’ı ve çözücü yüzdesinin birleştirilmiş etkisini incelemek amacıyla SVEA C18 (5 μm, 150 mm x 4.6 mm) YPSK analiz kolonu ve farklı oranda asetonitril-su (%30, %35 ve %40 (h/h)) ikili karışımlarından oluşan, farklı pH değerlerine (3,13-6,18) sahip hareketli fazlar kullanılmıştır. Asidik iyonlaşma sabitleri doğrusal olmayan regresyon modeli kullanılarak tahmin edilmiştir. Piroksikamın sudaki pKa değeri mol kesri-pKa yöntemiyle hesaplanmıştır. Veriler literatürde farklı tekniklerle elde edilmiş olanlarla kıyaslanmış ve uyumlu olduğu görülmüştür.

Keywords

pka, Piroksikam, Yüksek Performanslı Sıvı Kromatografisi

Determination of pKa Value of Piroxicam by High Performance Liquid Chromatography

Abstract

In this study, acid ionization constants (pKa) of piroxicam, a nonsteroidal anti-inflammatory drug, in different acetonitrile-water binary mixtures and water were determined by reverse phase liquid chromatography method. SVEA C18 (5 μm, 150 mm x 4.6 mm) HPLC analysis column and different ratios of acetonitrile-water (30%, 35%, and 40% (v/v)) binary mixtures with different pH values (3.13-6.18) were used to investigate the combined effect of pH of the mobile phase and percentage of solvent on the chromatographic behavior of piroxicam. Acidic ionization constants were estimated using a nonlinear regression model. The pKa value of piroxicam in water was calculated by the mole fraction- pKa method. The data were compared with values obtained by different techniques in the literature and were found to be compatible.

Keywords

pka, Piroxicam, High Performance Liquid Chromatography

References

• Avdeef, A., Box, K. J., Comer, J. E. A., Gilges, M., Hadley, M., Hibbert, C., Patterson, W. & Tam, K. Y. (1999). PH-metric log P 11. pKa determination of water-insoluble drugs in organic solvent–water mixtures. Journal of pharmaceutical and biomedical analysis, 20(4), 631-641. doi:https://doi.org/10.1016/S0731-7085(98)00235-0.
• Babić, S., Horvat, A. J., Pavlović, D. M., & Kaštelan-Macan, M. (2007). Determination of pKa values of active pharmaceutical ingredients. TrAC Trends in Analytical Chemistry, 26(11), 1043-1061.doi: https://doi.org/10.1016/j.trac.2007.09.004.
• Çelebier, M., Nenni, M., Kaplan, O., Akgeyik, E., Kaynak, M. S., & Şahİn, S. (2020). Determination of the Physicochemical Properties of Piroxicam. Turkish Journal of Pharmaceutical Sciences, 17(5), 535. doi:https://doi.org/10.4274/tjps.galenos.2019.82335.
• Demiralay, E. C., Alsancak, G., & Ozkan, S. A. (2009). Determination of pKa values of nonsteroidal antiinflammatory drug‐oxicams by RP–HPLC and their analysis in pharmaceutical dosage forms. Journal of separation science, 32(17), 2928-2936. doi:https://doi.org/10.1002/jssc.200900234.
• 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. doi: https://doi.org/10.1016/j.jpba.2012.06.023.
• Gwak, H. S., Choi, J. S., & Choi, H. K. (2005). Enhanced bioavailability of piroxicam via salt formation with ethanolamines. International journal of pharmaceutics, 297(1-2), 156-161. doi:https://doi.org/10.1016/j.ijpharm.2005.03.016.
• Ishihama, Y., Nakamura, M., Miwa, T., Kajima, T., & Asakawa, N. (2002). A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery. Journal of pharmaceutical sciences, 91(4), 933-942. doi:https://doi.org/10.1002/jps.10087.
• Moldoveanu, S. C., & David, V. (2002). Sample preparation in chromatography: Elsevier.
• Moldoveanu, S. C., & David, V. (2013a). Chapter 1 - Basic Information about HPLC. In S. C. Moldoveanu & V. David (Eds.), Essentials in Modern HPLC Separations (pp. 1-51): Elsevier.
• Moldoveanu, S. C., & David, V. (2013b). Chapter 7 - Mobile Phases and Their Properties. In S. C. Moldoveanu & V. David (Eds.), Essentials in Modern HPLC Separations (pp. 363-447): Elsevier.
• Rosés, M., Canals, I., Allemann, H., Siigur, K., & Bosch, E. (1996). Retention of Ionizable Compounds on HPLC. 2. Effect of pH, Ionic Strength, and Mobile Phase Composition on the Retention of Weak Acids. Analytical Chemistry, 68(23), 4094-4100. doi: https://doi.org/10.1021/ac960105d.
• Sezgin, B., Arli, G., & Can, N. Ö. (2021). Simultaneous HPLC-DAD determination of seven intense sweeteners in foodstuffs and pharmaceuticals using a core-shell particle column. Journal of Food Composition and Analysis, 97, 103768. doi:https://doi.org/10.1016/j.jfca.2020.103768.
• Skoog, D. A., Holler, F. J., & Crouch, S. R. (2017). Principles of instrumental analysis: Cengage learning.
• Snyder, L. R., Kirkland, J. J., & Dolan, J. W. (2011). Introduction to modern liquid chromatography: John Wiley & Sons.
• Soyseven, M., Kaynak, M. S., Çelebier, M., Aboul-Enein, H. Y., & Arli, G. (2020). Development of a RP-HPLC method for simultaneous determination of reference markers used for in-situ rat intestinal permeability studies. Journal of Chromatography B, 1147, 122150. doi:https://doi.org/10.1016/j.jchromb.2020.122150.
• Starek, M., & Krzek, J. (2009). A review of analytical techniques for determination of oxicams, nimesulide and nabumetone. Talanta, 77(3), 925-942. doi:https://doi.org/10.1016/j.talanta.2008.09.022.
• Subirats, X., Rosés, M., & Bosch, E. (2007). On the effect of organic solvent composition on the pH of buffered HPLC mobile phases and the pKa of analytes - A review. Separation and Purification Reviews, 36(3), 231-255. doi:https://doi.org/10.1080/15422110701539129.
• Tindall, G. W., & Dolan, J. W. (2003). Mobile-Phase Buffers, Part II-Buffer Selection and Capacity. LC GC Europe, 16, 10.