title: Simultaneous determination of LogD, LogP, and pK(a) of drugs by using a reverse phase HPLC coupled with a 96-well plate auto injector.
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 pK(a) 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 pK(a) value was determined by using the Polynomial fit between LogP and LogD and the equation LogD (pK(a)) approximately 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.
authors.affiliation: Global Research and Development, Pharmaceutical Research and Development, St. Louis Laboratories, Pfizer Inc, 700 Chesterfield Parkway N. T2F Chesterfield, MO, USA. Po-Chang.Chiang@pfizer.com
authors.forename: Po-Chang
authors.initials: PC
authors.lastname: Chiang
authors.forename: Yiding
authors.initials: Y
authors.lastname: Hu
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D008722:Methods; D046228:Microarray Analysis / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations