Quantitative retention-activity relationship models of angiotensin converting enzyme inhibitors using biopartitioning...

Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can simulate biopartioning process of many kinds of drugs and describe their biological behavior. The capability of BMC to describe and estimate pharmacokinetic and pharmacodynamic parameters of angiotensin-converting enzyme inhibitors (ACEIs) had been studied in this paper. The correlation between retention factors of ACEIs obtained using BMC and bioactivity parameters (half-life, volume of distribution, clearance, and IC(50)) was investigated utilizing a second-order polynomial model. The P-values obtained for half-life, volume of distribution, clearance, and IC(50) models were less than 0.05, and the r(2) of those four models were 0.89, 0.98, 0.94, and 0.97, with r(2)(adj) (adjusted for freedom degrees) being 0.85, 0.98, 0.91, and 0.95, respectively. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross-validated data [root mean squared error of calibration (RMSEC), root mean squared error of cross-validation (leave-one-out) (RMSECV), and root mean squared error of cross-validation (leave-one-out) for interpolated data (RMSECVi)]. The quantitative retention-activity relationship (QRAR) models of ACEIs developed in this paper may be a useful approach to screening new chemicals in the early stage of development.