Determination of Ionization Constant Value of Pravastatin in Water and Water-Acetonitrile Binary Mixtures by RPLC Method

Yıl 2023, , 145 - 151, 25.04.2023

Mehmet Emre Tanrıkulu , İlkay Konçe , Ebru Çubuk Demiralay

https://doi.org/10.19113/sdufenbed.1183285

Öz

Reverse phase liquid chromatography (RPLC) is preferred for the determination of ionization/protonation (pKa) constants of compounds containing acidic and basic functional groups. The pKa value is an important parameter to predict the absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of drugs. In this study, RPLC method was developed for the determination of pKa value of pravastatin in water-acetonitrile binary mixture and the chromatographic behavior of pravastatin was determined by changing the amount of acetonitrile in the mobile phase. The study was carried out in Nucleosil C4 (250×4,6 mm, 5 µm) column, at 37°C and at a constant flow rate of 1 mL/min. With the obtained retention data, the pKa of the compound was determined using nonlinear model. The pKa value of hydrophilic pravastatin in water was calculated using the mobile phase pKa values determined in different organic modifier-water mixtures and the macroscopic constants (mole fraction, dielectric constant, etc.) of acetonitrile, specific solvation interaction parameters between the solvent and the solute. It has been observed that this important physicochemical parameter calculated is compatible with the literature data.

Anahtar Kelimeler

RPLC, Carboxylic acid group, Ionization constant, Hydrophilic compound

Pravastatinin Su ve Su-Asetonitril İkili Karışımlarında İyonlaşma Sabiti Değerinin RPLC Metoduyla Belirlenmesi

Öz

Ters faz sıvı kromatografi (RPLC) yöntemi asidik ve bazik fonksiyonel grup içeren bileşiklerin iyonlaşma/protonasyon (pKa) sabitlerinin tayini için tercih edilmektedir. pKa değeri, ilaçların absorpsiyon, dağılım, metabolizma, atılım, toksitite (ADMET) özelliklerini tahmin etmeye yarayan önemli bir parametredir. Sunulan bu çalışmada, pravastatinin su-asetonitril ikili karışımında pKa değerinin tayini için RPLC metot geliştirilmiş ve asetonitrilin mobil fazdaki miktarının değişimiyle pravastatinin kromatografik davranışı da belirlenmiştir. Çalışma Nücleosil C4 (250×4,6 mm, 5 µm) kolonda, 37°C’de ve 1 mL/dakika sabit akış hızında gerçekleştirilmiştir. Elde edilen alıkonma verileriyle doğrusal olmayan model kullanılarak bileşiğin pKa değeri belirlenmiştir. Hidrofilik özellikte olan pravastatinin su ortamındaki pKa değeri farklı organik modifiyer-su karışımlarında tayin edilen mobil faz pKa değerleri ve asetonitrilin makroskopik sabitleri (mol kesri, dielektrik sabiti, vs.), çözücü-çözünen arasındaki spesifik solvasyon etkileşim parametreleri kullanılarak hesaplanmıştır. Hesaplanan bu önemli fizikokimyasal parametrenin literatür verileriyle uyumlu olduğu görülmüştür.

Anahtar Kelimeler

RPLC, Karboksilik asit grubu, İyonlaşma sabiti, Hidrofilik bileşik

Kaynakça

• [1] Süzer, Ö. ed. 2009. Tedavinin Farmakolojik Temeli. Nobel Tıp Kitabevleri, İstanbul, 2017s.
• [2] Brain-Isasi, S., Requena, C., Alvarez-Lueje, A., 2008. Stability Study of Pravastatin Under Hydrolytic Conditions Assessed by HPLC. J. Chil. Chem. Soc, 53(4), 1684-1688.
• [3] Prasanthi, T., Lakshmana, R. A., Reshma, P., Susanthi, P., Merwin, P., Ajay, P., 2022. Novel RP-HPLC Method Development and Validation for Estimation of Pravastatin in Pure and Pharmaceutical Formulation. Journal of Applied Pharmaceutical Sciences and Research, 4(3), pp. 13-17.
• [4] Shinde, A. C., Devhadrao, N. D., Bansode, A. S., Bansode, A. S.,Ajit S Bansode, 2019. Analytical Method Development and Validation of Assay Test of Pravastatin Sodium Tablets. Journal of Drug Delivery & Therapeutics, 9(2):70-75.
• [5] Maree, S., Preez, J. L., Plessis, L. H., Plessis, J., Gerber, M., 2020. A Novel HPLC Method Developed and Validated for the Detection and Quantification of Atorvastatin, Fluvastatin, Pitavastatin and Pravastatin During Transdermal Delivery Studies. Die Pharmazie - An International Journal of Pharmaceutical Sciences, 75 (5), 164-166.
• [6] Suntornsuk, L., Anurukvorakun, O., 2022. Sensitivity Enhancement in Capillary Electrophoresis and Their Applications for Analyses of Pharmaceutical and Related Biochemical Substances. Electrophoresis, 43,939–954. [7] Pınar Talay Pınar, Tamer Tuluk, Zühre Şentürk, Determination of Pravastatin Drug Formulation by Squarewave Voltammetry on Glassy Carbon Elektrode, Dokuz Eylül Üniversitesi Mühendislik Fakültesi Fen ve Mühendislik Dergisi 2020, 22 (64), 29-35.
• [8] Antal, I., Koneracka, M., Zavisova, V., Kubovcikova, M., Kormosh, Z., Kopcansky, P., 2017. Statins Determination: A Review of Electrochemical Techniques. Critical Reviews in Analytical Chemistry, 47:6, 474-489.
• [9] Kazakevich, Y., Lobrutto, Y., 2007. HPLC for Pharmaceutical Scientists, First ed., Wiley-Interscience, USA.
• [10] V.R. Meyer, Practical High-Performance Liquid Chromatography, Fifth ed., John Wiley and Sons, United Kingdom, 2010.
• [11] Bergés, R., Sanz-Nebot, V., Barbosa, J., 2000. Modelling Retention in Liquid Chromatography as a Function of Solvent Composition and pH of the Mobile Phase, J Chromatogr A, 869, 27-39.
• [12] Rosés, M., Bosch, E., 2002. Influence of Mobile Phase Acid–Base Equilibria on The Chromatographic Behaviour of Protolytic Compounds. Journal of Chromatography A, 982, 1–30.
• [13] Konçe, İ., Demiralay, E. Ç., Ortak, H. Y., 2019. Chromatographic Determination of Thermodynamic Acid Dissociation Constants of Tetracycline Antibiotics and Their Epimers. J Chromatogr Sci, 16;57(8):745-750.
• [14] 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(25), Pages 7-11.
• [15] Sun, N., Avdeef, A., 2011. Biorelevant pKa (37℃) Predicted from the 2D Structure of the Molecule and its pKa at 25°C. J. Pharm. Biomed. Anal, 56, 173– 182.
• [16] Tallarida, R. J., Murray, R. B., 1987. Henderson-Hasselbalch Equation, in: R.J. Tallarida, R.B. Murray (Eds.), Manual of Pharmacologic Calculations, Springer, New York, 1987, pp.74-75.
• [17] Mussini, T., Covington, A. K., Longhi, P., Rondinini, S., 1985. Criteria for Standardization of pH Measurements in Organic Solvents and Water + Organic Solvent Mixtures of Moderate to High Permittivities. Pure Appl Chem, 57(6): 865- 876.
• [18] SwissADME program. http://www.swissadme.ch /index.php (Erişim Tarihi: 25.09.2022).
• [19] NLREG Version 4.0. P.H. Sherrod. http://www.sandh.com/Sherrod.1991 (Erişim Tarihi: 27.09.2022). [20] Althanoon, Z., Ibrahim, M. F., Ahmad, A. A., Merkhan, M. M., 2020. Pharmacological Aspects of Statins Are Relevant to Their Structural and Physicochemical Properties Sys Rev Pharm 11(7):167-171.
• [21] 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.
• [22] Barbosa, J., Berges, R., Sanz-Nebot, V., 1998. Retention Behaviour of Quinolone Derivatives in High-Performance Liquid Chromatography Effect of pH and Evaluation of Ionization Constants, Journal of Chromatography A, 823 (1998) 411–422.
• [23] Poole, C. F., Poole, S. K., 1991. Chromatography Today. Elsevier Science B.V. Amsterdami, First Edition.
• [24] Barbosa, J., Toro, I., Sanz-Nebot, V., 1997. Acid-Base Behaviour of Tripeptides in Solvents Used in Liquid Chromatography. Correlation Between pK Values and Solvatochromic Parameters of Acetonitrile-Water Mixtures. Anal Chim Acta, 347(3): 295-304.
• [25] Motoo, Y., 1959. Dissociation Constants of Some Carboxylic Acids in Mixed Aqueous Solvents, Vol.32, No.5 429-432.
• [26] Espinosa, S., Bosch, E., Rosés, M., 2002. Retention of Ionizable Compounds in High-Performance Liquid Chromatography 14. Acid–Base pK Values in Acetonitrile–Water Mobile Phases. Journal of Chromatography A, 964, 55–66.
• [27] Talay, A., Demiralay, E. Ç., Daldal, Y. D., Üstün, Z., 2015. Investigation of Thermodynamic Acidity Constants of Some Statins with RPLC Method. Journal of Molecular Liquids, 208, 286–290.
• [28] Canseven, V., Demiralay, E. Ç., Üstün, Z., Daldal, Y. D., Özkan, S. A., Alsancak, G., 2016. Measurements of Thermodynamic Acid Dissociation Constants for Three HMG-CoA Reductase Inhibitors by using RPLC and Study of Validation in Pharmaceutical Tablets, Current Pharmaceutical Analysis, 12,1-8.
• [29] Ishihama, Y., Nakamuro, 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. J Pharm. Sci, 91(4), 933-942.