Development of Predictive Quantitative Retention-Activity Relationship Models of Quinolones by Mixed Micellar Liquid Chromatography / 中国药学杂志

ABSTRACT

OBJECTIVE: To obtain the adequate QRAR models of the half-life (t1/2), clearance(CL), volume of distribution (Vd) and area under concentration-time curve (AUC) of quinolones and elucidate the advantages and limitations of using mixed micellar liquid chromatography for describing and estimating the biological parameters. METHODS: The BMCBrij35/SDSQRAR models using mixed micellar system of Brij35/SDS (8515 ) as a mobile phase under adequate experimental conditions were developed for the biological parameter estimation of quinolones. The correlation between retention factors and biological activities was investigated using second order polynomial models. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross-validated data (RMSEC, RMSECV and RMSECVi). RESULTS: The BMCBrij35/SDSQRAR models of t1/2, CL, Vd and AUC were statistically significant and both interpolation and extrapolation of parameters were reasonably adequate. CONCLUSION: The mixed micellar liquid chromatography can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains, which may become a simple, economic, and highly reproducible option for establishing QRAR model.