Bhatt Nejal M, Chavada Vijay D, Sanyal Mallika, Shrivastav Pranav S
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
Department of Chemistry, St. Xavier's College, Navrangpura, Ahmedabad, Gujarat, India.
Biomed Chromatogr. 2019 Nov;33(11):e4666. doi: 10.1002/bmc.4666. Epub 2019 Sep 2.
Knowledge of the acid-base dissociation constants of drugs is the key to understanding their biopharmaceutical characteristics. In the present work, the effect of pH and organic modifiers (acetonitrile and methanol) was investigated in the determination of dissociation constants (pK ) of nine representative drugs (atenolol, betahistine, clarithromycin, deferiprone, diclofenac, ibuprofen, metoprolol, naproxen and propranolol) using reversed-phase thin-layer chromatography. Mobile phase consisting of various buffers and methanol-acetonitrile (10, 20, 30, 40, 50 and 60%, v/v) was used to evaluate the retention pattern on reversed-phase plates. Compared with methanol, acetonitrile gave better results for the experimentally determined pK values by extrapolation to zero organic modifier volume fractions. To assess the effectiveness of the developed method the results were correlated using principal component analysis and hierarchical cluster analysis. The calculated values of the aqueous dissociation constant were compared with those reported previously using potentiometry and capillary electrophoresis and also with different computational platforms like ACD/Lab, ChemAxon and Jchem calculator. The results obtained by the RPTLC method were in good agreement with potentiometric methods for pK determination.
了解药物的酸碱解离常数是理解其生物药剂学特性的关键。在本研究中，采用反相薄层色谱法研究了pH值和有机改性剂（乙腈和甲醇）对九种代表性药物（阿替洛尔、倍他司汀、克拉霉素、去铁酮、双氯芬酸、布洛芬、美托洛尔、萘普生和普萘洛尔）解离常数（pK）测定的影响。使用由各种缓冲液和甲醇 - 乙腈（10%、20%、30%、40%、50%和60%，v/v）组成的流动相来评估反相板上的保留模式。与甲醇相比，通过外推至零有机改性剂体积分数，乙腈在实验测定的pK值方面给出了更好的结果。为了评估所开发方法的有效性，使用主成分分析和层次聚类分析对结果进行了关联。将计算得到的水解离常数与先前使用电位滴定法和毛细管电泳法报道的值以及不同的计算平台（如ACD/Lab、ChemAxon和Jchem计算器）得到的值进行了比较。通过反相薄层色谱法获得的结果与电位滴定法测定pK的结果高度一致。
