DETERMINATION OF CHROMATOGRAPHIC PROTONATION CONSTANTS OF SOME IMIDAZOLE ANTIMYCOTIC DRUGS IN ACETONITRILE-WATER BINARY MIXTURES

Year 2022, Volume: 46 Issue: 2, 405 - 417, 29.05.2022

Hayrettin Seçilmiş , Ebru Çubuk Demiralay , Kader Poturcu

https://doi.org/10.33483/jfpau.1081989

Cited By: 1

Abstract

Objective: In this study, the thermodynamic protonation constant ((_s^s)〖pK〗_a ) of antifungal azole derivative miconazole and tioconazole were investigated by the reversed-phase liquid chromatography (RPLC) method. Although classical stationary phases are the most commonly used column-packed materials in the analyses of these compounds by the RPLC method, the determination of the pKa value of miconazole and tioconazole with a cyano-based column has not been reported so far.

Material and Method: Chromatographic behavior of the selected compounds was determined with Ultra Cyano column (Restek®, 150×3.0 mm I.D, 3µm) which is compatible with hydrophobic compounds. The dependence of the retention times on the acetonitrile content of the mobile phase and the effect of the mobile phase pH on the chromatographic retention was determined for each compound by changing the pH in the range of 3.0-7.50.

Result and Discussion: The (_s^s)〖pK〗_a values were determined by a nonlinear regression program. The thermodynamic aqueous pKa ((_w^w)〖pK〗_a ) value of the studied compounds was calculated from the (_s^s)〖pK〗_a value by using the macroscopic parameters (dielectric constant and mole fraction) that play an important role in the solvent properties. The calculated (_w^w)〖pK〗_a values were compared with literature values.

Keywords

Combined effect, Imidazole, Nonlinear regression, RPLC

Thanks

We acknowledge Dr. Jose Luis Beltran (University of Barcelona) for kindly providing the NLREG 4.0 program.

ASETONİTRİL-SU İKİLİ KARIŞIMLARINDA BAZI İMİDAZOL ANTİMİKOTİK İLAÇLARIN KROMATOGRAFİK PROTONASYON SABİTLERİNİN BELİRLENMESİ

Abstract

Amaç: Bu çalışmada, antifungal azol türevi mikonazol ve tiokonazolün termodinamik protonasyon sabiti ((_s^s)〖pK〗_a ) ters faz sıvı kromatografisi (RPLC) yöntemi ile araştırılmıştır. Bu bileşiklerin RPLC yöntemi ile analizlerinde klasik sabit fazlar en yaygın olarak kullanılan kolon dolgulu malzemeler olmasına rağmen, siyano bazlı bir kolonla şimdiye kadar mikonazol ve tiokonazolün pKa değerinin tayini rapor edilmemiştir.

Gereç ve Yöntem: Seçilen bileşiklerin kromatografik davranışları hidrofobik bileşiklerle uyumlu Ultra siyano kolon (Restek®, 150×3.0 mm I.D, 3µm) ile belirlenmiştir. Alıkonma sürelerinin mobil fazın asetonitril içeriğine bağımlılığı ve mobil faz pH'ının kromatografik alıkonma üzerindeki etkisi, pH 3.0-7.50 aralığında değiştirilerek her bir bileşik için belirlenmiştir.

Sonuç ve Tartışma: (_s^s)〖pK〗_a değerleri, doğrusal olmayan bir regresyon programı ile belirlenmiştir. Çalışılan bileşiklerin termodinamik suda pKa ((_w^w)〖pK〗_a ) değeri, çözücü özelliklerinde önemli bir rol oynayan makroskopik parametreler (dielektrik sabiti ve mol fraksiyonu) kullanılarak (_s^s)〖pK〗_a değerinden hesaplanmıştır. Hesaplanan (_w^w)〖pK〗_a değerleri literatür değerleri ile karşılaştırılmıştır.

Keywords

Birleşik etki, İmidazol, Nonlineer regresyon, RPLC

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