中药复方祛瘀化痰通脉方在小型猪体内的药代动力学行为研究

目的 探讨祛瘀化痰通脉方（QYHT）在假手术组和模型组小型猪体内药代动力学特征,为QYHT的药效物质基础研究及临床应用提供参考。方法 采用高脂饲料喂养结合冠状球囊拉伤内皮损伤的方法建立痰瘀互结证冠心病小型猪模型,连续给药8周后不同时间点取血,对血浆中各成分的浓度进行测定,并计算药代动力学参数。结果 建立了小型猪血浆中9个成分含量测定方法,经方法学验证,专属性、线性范围、准确度和精密度、提取回收率、稳定性以及基质效应均符合体内药物分析的要求。给药后假手术组可检测到3个入血成分,模型组检测到5个入血成分。 结论 QYHT在假手术组和模型组动物体内的处置过程存在一定差异。该测定方法适用于检测QYHT在小型猪血浆中的药代动力学研究,可为该复方的临床合理安全用药提供科学参考。

Pharmacokinetic Behavior Research of Quyuhuatantongmai Formula in Miniature Swine

Objective To investigate the material foundation and provide reference for clinical application, a HPLC-MS/MS method was established to determine plasma concertration of main components from Quyu Huatan Tongmai(QYHT) formula extract in miniature swine plasma.Methods Phlegm-stasis syndrome of coronary heart disease was established by high-fat feeding and coronary intervention balloon injury. After 8 weeks of administration, blood samples were taken at the corresponding time points. The drug concentrations in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of plasma were calculated.Results The LC-MS/MS method for the determination of 9 components in miniature swine plasma was established. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability was validated. After administration of QYHT, 3 components were determinated in plasma of sham operation group, and 5 components were determinated in plasma of model group.Conclusion QYHT has a certain difference in the treatment process between sham and model animals. This LC-MS/MS analysis method established in this study was proved to be applied to the pharmacokinetic study of applied to the pharmacokinetic study of miniature swine after oral administration of QYHT, which could provide scientific reference for the safety of clinical rational use.