目的 研究使用混合胶束流动相建立喹诺酮类抗生素定量保留-活性关系(QRAR)模型的优点与不足。方法 在生物分配胶束色谱的单一流动相中加入十二烷基硫酸钠形成混合胶束溶液(Brij35/SDS),根据混合胶束色谱(BMCBrij35/SDS)中所得容量因子(k)建立各参数的QRAR模型,并对模型进行自身评价。 结果 t1/2,CL,Vd和 AUC的BMCBrij35/SDS-QRAR模型在置信度95％的水平上有统计学意义(P<0.05),模型预测能力较优。结论 使用BMCBrij35/SDS建立喹诺酮类抗生素的定量保留-活性关系模型是可行的。混合胶束能够更好的模拟生理条件下细胞膜与药物之间的各种作用力,在药物分离及模拟生物膜研究领域具有广泛的应用前景。
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/SDS-QRAR models using mixed micellar system of Brij35/SDS (85∶15) 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/SDS-QRAR 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.
关键词
定量保留-活性关系 /
生物分配胶束液相色谱 /
混合胶束流动相 /
喹诺酮类抗生素
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Key words
quantitative retention-activity relationship /
biopartioning micellar chromatography /
mixed micellar system /
quinolone
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中图分类号：
R917
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参考文献
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