DETERMINATION OF THE CHROMATOGRAPHIC IONIZATION CONSTANT VALUE OF THE POPULAR DIURETIC DRUG HYDROCLOROTHIAZIDE

Yıl 2024, Cilt: 48 Sayı: 1, 169 - 178, 20.01.2024

Yaşar Doğan Daldal , Ebru Çubuk Demiralay

https://doi.org/10.33483/jfpau.1346354

Öz

Objective: Hydrochlorothiazide is a drug that lowers blood pressure by decreasing Na+ and Cl- levels while increasing the rate and volume of urine excretion. This drug is used alone or in combination with other antihypertensive medications. However, the action mechanism of such an important drug is unknown, and in the literature, there is only one study on the value of the ionization constant of the compound in hydroorganic systems and no study on the value of the ionization constant of the compound in water. Therefore, in this study, an attempt was made to determine the ionization constant of hydrochlorothiazide in various binary acetonitrile-water mixtures and to determine the ionization constant of hydrochlorothiazide in water by using these values through various extrapolation methods.
Material and Method: The ionization constant of hydrochlorothiazide was determined in a binary mixture of 11%, 13%, and 15% (v/v) acetonitrile and water at 30oC, a flow rate of 1 ml/min, and an X Terra C18 column. To determine the ionization constant of hydrochlorothiazide, the pH retention relationship was evaluated using the linear solvation energy relationship (LSER) model. To determine the ionization constant values in water, the data obtained from the LSER model were evaluated using the Yasuda-Shedlowsky method and the mole fraction- (_s^s)〖pK〗_a method.
Result and Discussion: The agreement between the thermodynamic (_w^w)〖pK〗_(a_1 ) values calculated by the two methods is remarkable and consistent with those found in the literature for the organic solvent-water environment. Considering this information, the accuracy and reproducibility of the determined (_w^w)〖pK〗_(a_1 ) value of hydrochlorothiazide becomes clear. Moreover, the determined values are the first thermodynamic (_w^w)〖pK〗_(a_1 ) data in the literature obtained by any analytical method for hydrochlorothiazide.

Anahtar Kelimeler

Hydrochlorothiazide, LSER model, RPLC, the determination of the ionization constant

POPÜLER DİÜRETİK İLAÇ HİDROKLOROTİAZİDİN KROMATOGRAFİK İYONLAŞMA SABİTİ DEĞERİNİN BELİRLENMESİ

Öz

Amaç: Hidroklorotiazid, idrar çıkışının hızını ve hacmini arttırırken, Na+ ve Cl- içeriğini azaltarak kan basıncını düşüren bir ilaçtır. Bu ilaç, tek başına ya da diğer hipertansif ilaçlarla beraber kullanılmaktadır. Ancak, bu kadar önem arz eden bir ilacın etki mekanizması tam olarak bilinmemekle birlikte, bileşiğin hidro-organik sistemlerdeki iyonlaşma sabiti değeriyle alakalı literatürde sadece bir çalışma ve bileşiğin sudaki iyonlaşma sabiti değeriyle alakalı hiç çalışma yoktur. Bu nedenle bu çalışmada, farklı asetonitril-su ikili karışımlarında hidroklorotiazidin iyonlaşma sabiti değerlerinin tayini ve bu değerler kullanılarak çeşitli ekstrapolasyon yöntemleriyle hidroklorotiazidin su ortamındaki iyonlaşma sabiti değerinin tayini amaçlanmıştır.
Gereç ve Yöntem: Hidroklorotiazidin iyonlaşma sabiti tayini %11, %13 ve %15 (h/h) asetonitril-su ikili karışımında 30oC’de, 1 ml/dakika akış hızında ve X Terra C18 kolonda gerçekleştirilmiştir. Hidroklorotiazidin iyonlaşma sabitinin belirlenmesi için pH-alıkonma ilişkisi, lineer solvasyon enerjisi ilişkisi (LSER) modeliyle değerlendirilmiştir. Sudaki iyonlaşma sabiti değerlerinin tayini için LSER modelinden elde edilen veriler, Yasuda-Shedlovsky ve mol kesri-(_s^s)〖pK〗_a yöntemiyle değerlendirilmiştir.
Sonuç ve Tartışma: Her iki metotla hesaplanan termodinamik (_w^w)〖pK〗_(a_1 ) değerlerinin birbiriyle uyumu dikkat çekicidir ve literatürdeki organik çözücü-su ortamında elde edilen değerle uyumludur. Bu bilgiler ışığında, hidroklorotiazidin tayin edilen (_w^w)〖pK〗_(a_1 ) değerinin doğruluğu ve tekrarlanabilirliği açıkça görülmektedir. Ayrıca, tayin edilen değerler hidroklorotiazidin herhangi bir analitik yöntemle tayin edilen literatürdeki ilk termodinamik (_w^w)〖pK〗_(a_1 ) verileridir.

Anahtar Kelimeler

Hidroklorotiazid, iyonlaşma sabiti tayini, LSER modeli, RPLC

Kaynakça

• 1. Kayaalp, O., (2000). Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, Hacettepe-Taş Kitapçılık Ltd. Şti, Ankara, p.880.
• 2. Katzung, B.G., (2011). Basic & Clinical Pharmacology, The McGraw-Hill Companies, San Francisco, p.1245.
• 3. Laurence, L.B. (2009). Goodman & Gillman Tedavinin Farmakolojik Temeli, Nobel Tıp Kitabevi, Ankara, p.2017.
• 4. Manallack, D.T., Prankerd, R.J., Yuriev, E., Oprea, T.I., Chalmers, D.K. (2013). The significance of acid/base properties in drug discovery. Chemical Society Reviews, 42(2), 485-496. [CrossRef]
• 5. Manallack, D.T. (2007). The pKa distribution of drugs: Application to drug discovery. Perspectives in Medicinal Chemistry, 1, 25-38. [CrossRef]
• 6. Gaohua, L., Miao, X., Dou, L. (2021). Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity. Expert Opinion On Drug Metabolism & Toxicology,17(9), 1103-1124. [CrossRef]
• 7. Daldal, Y.D., Demiralay, E.Ç. (2022). Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pKa values of folic acid antimetabolites. Journal of Pharmaceutical and Biomedical Analysis, 212, 1-8. [CrossRef]
• 8. Daldal, Y.D., Demiralay, E.Ç. (2020). Chromatographic and UV-visible spectrophotometric pKa determination of some purine antimetabolites. Journal of Molecular Liquids, 317, 1-8. [CrossRef]
• 9. Kazakevich, Y., Lobrutto, Y. (2007). HPLC for Pharmaceutical Scientists, Wiley-Interscience, Canada, p.1135.
• 10. Meyer, V.R. (2010). Practical High-Performance Liquid Chromatography, John Wiley and Sons, Ltd., United Kingdom, p.428.
• 11. Babić, S., Horvat, A.J.M., Pavlović, D.M., Kaštelan-Macan, M. (2007). Determination of pKa values of active pharmaceutical ingredients. Trends in Analytical Chemistry, 26(11), 1043-1061. [CrossRef]
• 12. Beltrán, J.L., Sanli, N., Fonrodona, G., Barrón, D, Özkan, G., Barbosa, J. (2003). Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic acids in water and acetonitrile-water media. Analytica Chimica Acta, 484, 253-264. [CrossRef]
• 13. Daldal, Y.D., Çakır, C., Yılmaz, H., Demiralay, E.Ç., Özkan, S.A., Alsancak, G. (2014). Liquid chromatographic, spectrophotometric and potentiometric pKa determination of ranitidine and famotidine. Current Drug Therapy, 9, 277-284. [CrossRef]
• 14. Jiménez-Lozano, E., Marqués, I., Barrón, D., Beltrán, J.L., Barbosa, J. (2002). Determination of pKa values of quinolones from mobility and spectroscopic data obtained by capillary electrophoresis and a diode array detector. Analytica Chimica Acta, 464, 37-45. [CrossRef]
• 15. Barbosa, J., Barrón, D., Jiménez-Lozano, E., Sanz-Nebot, V. (2001). Comparison between capillary electrophoresis, liquid chromatography, potentiometric and spectrophotometric techniques for evaluation of pKa values of zwitterionic drugs in acetonitrile-water mixtures. Analytica Chimica Acta, 437, 309-321. [CrossRef]
• 16. Bosch, E., Espinosa, S., Rosés, M. (1998). Retention of ionizable compounds on high-performance liquid chromatography III. variation of pK values of acids and pH values of buffers in acetonitrile-water mobile phases. Journal of Chromatography A, 824, 137-146. [CrossRef]
• 17. Rosés, M., Bolliet, D., Poole, C.F. (1998). Comparison of solute descriptors for predicting retention of ionic compounds (phenols) in reversed-phase liquid chromatography using the solvation parameter model. Journal of Chromatography A, 829, 29-40. [CrossRef]
• 18. Li, J. (2002). Prediction of internal standards in reversed-phase liquid chromatography III. Evaluation of an alternative solvation parameter model to correlate and predict the retention of ionizable compounds. Journal of Chromatography A, 982, 209-223. [CrossRef]
• 19. Haque, S.K.M. (2022). Box-Behnken experimental design for optimizing the HPLC method to determine hydrochlorothiazide in pharmaceutical formulations and biological fluid. Journal of Molecular Liquids, 352, 1-12. [CrossRef]
• 20. Tiris, G., Mehmandoust, M., Lotfy, H.M. Erk, N., Joo, S.W., Dragoi, E.N., Vasseghian, Y. (2022). Simultaneous determination of hydrochlorothiazide, amlodipine, and telmisartan with spectrophotometric and HPLC green chemistry applications. Chemosphere, 303, 1-9. [CrossRef]
• 21. Shah, K. (2022). Simultaneous estimation of nebivolol hydrochloride and hydrochlorothiazide in tablets. International Journal of Pharmaceutical Research & Allied Sciences, 11(3), 34-39. [CrossRef]
• 22. Raut, P.V., Padwal, S.L., Bachute, M.T., Polshettiwar, S.A. (2021). Development and validation of RP-HPLC chromatographic dissolution method for the simultaneous estimation of ramipril and hydrochlorothiazide from solid dosage formulation. Journal of Pharmaceutical Research International, 33(42B), 203-217. [CrossRef]
• 23. Baek, K., Jeon, S.B., Kim, B.K., Kang, N.S. (2018). Method validation for equilibrium solubility and determination of temperature effect on the ionization constant and intrinsic solubility of drugs. Journal of Pharmaceutical Sciences & Emerging Drugs, 6(1), 1-6. [CrossRef]
• 24. Barbosa, J., Barrón, D., Jiménez-Lozano, E., Sanz-Nebot, V. (2001). Comparison between capillary electrophoresis, liquid chromatography, potentiometric and spectrophotometric techniques for evaluation of pKa values of zwitterionic drugs in acetonitrile-water mixtures. Analytica Chimica Acta, 437, 309–321. [CrossRef]
• 25. Sanli, S., Sanli, N., Alsancak, G. (2009). Determination of protonation constants of some tetracycline antibiotics by potentiometry and LC methods in water and acetonitrile- water binary mixtures. Journal of the Brazilian Chemical Society, 20, 939-946. [CrossRef]
• 26. Espinosa, S., Bosch, E., Rosés, M. (2002). Acid-base constants of neutral bases in acetonitrile–water mixtures. Analytica Chimica Acta, 454, 157-166. [CrossRef]
• 27. 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. [CrossRef]
• 28. Herrero-Martínez, J.M., Repollés, C., Bosch, E., Rosés, M., Ràfols, C. (2008). Potentiometric determination of aqueous dissociation constants of flavonols sparingly soluble in water. Talanta, 74, 1008-1013. [CrossRef]