Development of predictive quantitative retention-activity relationship models of HMG-CoA reductase inhibitors by biopartitioning micellar chromatography.
Biological fluid cell membranes are barriers for the uptake of many kinds of drugs and their metabolites, along with passive transport across membranes and bioaccumulation. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to simulate the drug's passive absorption and the transport in biological systems. The use of micellar aqueous solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of barbiturates, benzodiazepines, catecholamines, local anesthetics, non-steriodal anti-inflammatory drugs and tricyclic antidepressants. In this study, the relationships between the capacity factor in BMC and some pharmacokinetic and pharmacodynamic parameters of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are studied. Predictive quantitative retention-activity relationship (QRAR) models describing some of the biological activities and pharmacokinetic properties of HMG-CoA reductase inhibitors are obtained. The results indicate that QRAR model may be a useful tool during the drug discovery process.
Wang
Shu-Rong
SR
Department of Pharmacy, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.
Chen
Yu
Y
Wu
Li-Ping
LP
Miao
Wen-Juan
WJ
Xiong
Mei-Jin
MJ
Chen
Cong
C
Zhong
Zhi-Rong
ZR
Ye
Li-Ming
LM
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis*; D021281:Quantitative Structure-Activity Relationship; D012015:Reference Standards
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors