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

Year 2024, Volume: 48 Issue: 1, 169 - 178, 20.01.2024

Yaşar Doğan Daldal , Ebru Çubuk Demiralay

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

Abstract

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.

Keywords

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

POPÜLER DİÜRETİK İLAÇ HİDROKLOROTİAZİDİN KROMATOGRAFİK İYONLAŞMA SABİTİ DEĞERİNİN BELİRLENMESİ

Abstract

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.

Keywords

Hidroklorotiazid, iyonlaşma sabiti tayini, LSER modeli, RPLC

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