酸浆苦素L在大鼠体内的药动学研究

Pharmacokinetic of Physalin L in Rat Plasma

目的建立一种特异、灵敏、快速地检测酸浆苦素L在大鼠体内的药动学特征的LC-MS/MS方法。方法采用Waters XBridgetm-C18色谱柱(4.6 mm×150 mm,3.5μm),含有0.1%甲酸的水溶液-乙腈(45︰55)为流动相,等度洗脱,流速为0.6 m L·min^(-1)。采用负离子模式、MRM模式进行检测。结果酸浆苦素L浓度在0.492~493 ng·mL^(-1)与峰面积呈良好线性关系,最低定量限为0.492 ng·mL^(-1);批间、批内RSD均<7.86%,平均回收率为99.23%~106.73%,方法重复性良好。药动学结果表示,每只SD雄性大鼠灌胃2.0 mg酸浆苦素L后,酸浆苦素L在大鼠体内平均达峰时间tmax为0.69 h,平均药峰浓度Cmax为77.48 ng·mL^(-1),药时曲线下面积AUC0→t为280.78 ng·h·mL^(-1),平均半衰期t1/2为2.89 h。结论本研究探明了酸浆苦素L在大鼠体内的药动学特征,为锦灯笼在动物体内的血药监测提供了一个新的指标,利于研究人员对锦灯笼(尤其是酸浆苦素类化合物)药理活性与药动学的深入研究。

OBJECTIVE To establish a specific, sensitive, efficient method for the quantitative determination ofphysalin L in rats plasma using LC-MS/MS system, and provide a detection means for its pharmacokinetic characteristic. METHODS The separation of physalin L was performed on a Waters XBridgetm-Cls column （4.6 mm×l50 mm, 3.5 mm） with a mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile （45 ＂ 50）. The assay was based on a negative MRM scan. RESULTS The linear range of the calibration curve （0.492-493 ng.mL-1） was obtained with a good correlation coefficient. The lower limit of quantification was 0.492 ng.mL-1. The average recovery was 99.23%-106.73% and the RSD of intra- and inter-day precision were 〈7.86%. The repeatability of the method was good. After intragastric administration of 2.0 mg physalin L to each rat, the mean peak time （tmax） was 0.69 h and the meanmaximum concentration （Cmax） was 77.48 ng.mL-1. The area under the curve （AUC0t） was 280.78 ng·h·mL-1, its tl/2 was 2.89 h. CONCLUSION This study provides the physalin L characteristics of pharmacokinetics in rats, whitch is good for researchers on Physalis Calyx Sea Fructus （especially physalin comoounds） in-depth study of pharmacolozical activity and oharmacokinetics.