Study On The Predictive Quantitative Retention-activity Relationship Models Of ACEIs And Statins By Biopartitioning Micellar Chromatography

In the early stage of drug discovery, it's necessary to study the pharmacokinetic and pharmacodynamic properties of drug candidates.The studies have traditionally been conducted in living systems such as mice,rabbits,dogs,etc.With the development of combinatorial chemistry ,hundreds and hundreds of drugs that could show potential activity are synthesized .It's urgent to develop in vitro methodologies for the estimation of pharmacokinetic and pharmacodynamic parameters of new compounds as complementary tools to conventional classic methodologies. The main purpose of these methodologies can reduce costs and shorten time from drug discovery to drug market and lessen the use of experimentation animals.The use of quantitative structure-activity relationship(QSAR) can be served as an alternative of in vivo methodologies.The application of chromatographic parameters in QSAR give rise to a new field, namely,quantitative retention-activity relationship (QRAR). In this study, QRAR models of ACEIs and statins are developed by using biopartioning micellar chromatography(BMC).The retention data of ACEIs and statins were obtained in BMC,then capacity factor were calculated.Physical parameters values such as logP, pK_a and bioactivity parameters such as t_1/2 ,CL, Vd, IC₅₀ were taken from literatures.And then adequate QSRR and QRAR models were used to fit these data. Statistical parameters such as r²,r_adj², standard error(S.E) were used to evaluate these models' fitting results. RMSEC (the root mean square error of calibration) , RMSECV[the root mean square error of cross-validation (leave-one-out)], RMSECVi [the root...