Determination of Thermodynamic Protonation Constants of Some Selective Serotonin Reuptake Inhibitors in Water-Acetonitrile Binary Mixtures

Year 2022, Volume: 22 Issue: 5, 979 - 988, 27.10.2022

Yaşar Doğan Daldal , Ebru Çubuk Demiralay

https://doi.org/10.35414/akufemubid.1126047

Abstract

In this study, the retention behaviour of citalopram, fluvoxamine, and sertraline, selective serotonin reuptake inhibitors (SSRIs) used as alternatives to tricyclic antidepressants, was investigated in a binary water-acetonitrile mixture by reverse-phase liquid chromatographic (RPLC) method. Chromatographic analyzes were performed in binary acetonitrile-water mixtures with mobile phase pH ranging from 6.5 to 10.5 and acetonitrile content between 45% and 55% (v/v). Throughout the study, the column temperature and flow rate were fixed at 30 °C and 0.8 mL/min, respectively. In this study, the theoretical retention values were calculated by evaluating the retention values of the compounds against the pH values of the mobile phase using the linear solvation energy relationship (LSER) approach. In addition, the thermodynamic protonation constants ((_s^s)〖pK〗_a) of the compounds were determined with a nonlinear regression program, considering the activity coefficients of the mobile phases at different pH values. Using the (_s^s)〖pK〗_a values of the hydrophobic compounds, the values of the protonation constants in the water medium were calculated using two different approaches. At the end of the study, it was found that the results obtained by both extrapolation methods were compatible with each other.

Keywords

Selective Serotonin reuptake Inhibitor, Thermodynamic Protonation constant, Retention behaviour, Binary mixture of water-acetonitrile

Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi

Abstract

Bu çalışmada, trisiklik antidepresanlara alternatif olarak kullanılan selektif serotonin geri alım inhibitörleri (SSRİ)’nden sitalopram, fluvoksamin ve sertralinin su-asetonitril ikili karışımında, ters faz sıvı kromatografik (RPLC) yöntemle alıkonma davranışı incelenmiştir. Kromatografik analizler, mobil faz pH’sı 6,5 ila 10,5 arasında değişen, %45-%55 (h/h) arasında asetonitril içeren asetonitril-su ikili karışımlarında gerçekleştirilmiştir. Çalışma boyunca, kolon sıcaklığı ve akış hızı sırasıyla, 30 oC ve 0,8 mL/dakika’da sabitlenmiştir. Bu çalışmada, mobil faz pH değerlerine karşı bileşiklerin alıkonma değerlerinin lineer solvasyon enerjisi ilişkisi (LSER) yaklaşımıyla değerlendirilmesiyle teorik alıkonma değerleri hesaplanmıştır. Ayrıca farklı pH değerlerindeki mobil fazların aktivite katsayıları değerleri hesaba katılarak doğrusal olmayan regresyon programıyla bileşiklerin termodinamik protonasyon sabitleri ((_s^s)〖pK〗_a) belirlenmiştir. Hidrofobik özellikteki bileşiklerin (_s^s)〖pK〗_a değerleri kullanılarak iki farklı yaklaşımla su ortamındaki protonasyon sabiti değerleri hesaplanmıştır. Çalışma sonunda her iki ekstrapolasyon yönteminden elde edilen sonuçların birbiriyle uyumlu olduğu görülmüştür.

Keywords

Selektif serotonin geri alım inhibitörü, Termodinamik protonasyon sabiti, Alıkonma davranışı, Su-asetonitril ikili karışımı

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• İnternet Kaynakları 1- http://www.chemicalize.org, (01.06.2022)