UPLC-MS/MS 法及体外溶出/吸收仿生系统法对异欧前胡素药代动力学特征的研究
 

摘要：目的 研究中药白芷中主要成分异欧前胡素体内药代动力学特征及生理因素对其体内过程的影响。方法 建立超高效液相色谱质谱联用方法（UPLC-MS/MS），测定灌胃给药后大鼠血浆中异欧前胡素血药浓度变化，同时考察异欧前胡素在不同pH 下的稳定性以及采用体外方法考察异欧前胡素的溶出性能；结果 建立了UPLC-MS/MS 法测定大鼠血浆中的异欧前胡素浓度，并用于其药代动力学研究。质谱条件：采用电喷雾离子源（ESI），正离子检测，监测离子为271.02→202.9（异欧前胡素）和216.9→173.7（佛手柑内酯，内标），该方法准确度、精密度、回收率、线性范围皆符合要求；经非房室模型拟合后其数据表明异欧前胡素在体内分布广泛（Vz/F = 543.7 ± 4.79 L/kg）、血药浓度水平低（Cmax = 0.26 ± 0.002 μg/mL）、代谢慢；在酸性和碱性溶液中异欧前胡素均不稳定、发生降解；溶出实验表明异欧前胡素溶出缓慢，水溶性差（累积溶出率 = 0.046 ± 0.02 %）；结论 建立的UPLC-MS/MS方法专属性强，灵敏度高，可用于异欧前胡素的体内定量分析；以及白芷中有效成分异欧前胡素在体内血药浓度低，可能由于其在胃酸溶液中不稳定、胃肠道中溶出量少所导致。
 

关键词：异欧前胡素；白芷；体外药物溶出/吸收仿生系统（DDASS）；UPLC-MS/MS

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