Abstract
For years, the physicochemical properties of drug candidates have been used to predict their in vivo pharmacokinetic behaviors. Several theories and empirical correlations have been established by various researchers with the overall goal of expediting the drug candidate selection process, with greater confidence and faster turnaround. This study describes a 96-well reverse phase HPLC method, simultaneously determining LogD, LogP, and pKa values of drugs in a throughput mode. The LogD and LogP values of each compound were determined, based on the octanol-aqueous partitioning behavior of the charged and non-charged species under different pH values. The pKa value was determined by using the Polynomial fit between LogP and LogD and the equation LogD (pKa) ≉ LogP – 0.301. The advantages of this method are: low sample consumption, suitability for low solubility compounds, less restriction on compound purity, potential for higher throughput, precise data, and multiple determinations in one assay.
Keywords: LogD, LogP, pKa, drug candidates, reverse phase HPLC, in vivo
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Current Computer-Aided Drug Design
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