生物胶束液相色谱中黄酮类化合物定量保留.docVIP

生物胶束色谱中黄酮类化合物定量保留-药动学性质预测模型的研究 沈继斌1, 2，佟巍2，崔颖2, 3*，李灵芝2, 3* （1. 天津医科大学药学院，天津 300070；2. 武警后勤学院 药物化学教研室，天津 300162；3. 天津市职业与环境危害防制重点实验室，天津 300162） [摘要] 目的 利用生物胶束色谱（Biopartitioning Micellar Chromatography, BMC）建立黄酮类化合物保留-药动学性质定量关系（quantitative retention activity relationship, QRAR）预测模型。方法 测定化合物在pH7.4的 0.05M Brij 35缓冲盐流动相中的保留时间并计算保留因子，对保留因子与文献报道药代动力学参数进行拟合，建立QRAR模型，并对模型相关性和预测能力进行评价。结果 半衰期（T1/2）、表观分布容积（Vd）和总清除率（Cl）的QRAR模型在置信度99%的水平上有统计学意义（P0.05），交叉验证结果符合预测性能统计学要求。结论 构建的黄酮类化合物药代动力学性质QRAR模型具有较好的相关性和预测性能。 [关键词] 生物胶束色谱；定量保留-药动学活性关系；黄酮 [中图法分类号] R914.1；R914.2 Study on Quantitative Retention-Pharmacokinetic Activity Relationship Models of Flavonoids by Biopartitioning Micellar Chromatography Shen Jibin1, 2, Tong Wei2, Cui Ying2, 3*, Li Lingzhi2, 3*(1 College of Pharmacy, Tianjin Medical University, Tianjin, 300070, 2 Department of Medicine Chemistry, Logistics College of Chinese People’s Armed Police Forces, Tianjin, 300162; 3 Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental harzard, Tianjin, 300162) [Abstract] Objective To develop the quantitative retentionactivity relationship (QRAR) models by biopartitioning micellar chromatography(BMC) for estimating the pharmacokinetic parameters of flavonoids. Methods The retention time of the flavonoids in the pH 7.4 0.05M Brij 35 mobile phases were determined, and the retention data of flavonoids and their corresponding properties were adjusted to second-order polynomial QRAR model，then the model interpretative and predictive ability were evaluated. Results The QRAR models of T1/2, Vd and Cl obtained in physiological conditions were statistically significant and perfect prediction. Conclusion The pharmacokinetic QRAR models obtained using the retention data of flavonoids show good interpretative and predictive ability. [Key words] biopartitioning micellar chromatography; quantitative retention- pharmacokinetic activity relationship; flavonoids Corresponding author: Cui Ying； Li Lingzhi Telephone:86-022