酸浆苦素L在大鼠体内的药动学研究

Pharmacokinetic of Physalin L in Rat Plasma

关键词:  酸浆苦素L  液质联用  定量分析  药动学

Key words:  physalin L  LC-MS/MS  quantitative analysis  pharmacokinetic

摘要:

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，3.5 μm），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 mL·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t_max为0.69 h，平均药峰浓度C_max为77.48 ng·mL^-1，药时曲线下面积AUC_0→t为280.78 ng·h·mL^-1，平均半衰期t_1/2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。

Abstract:

OBJECTIVE To establish a specific, sensitive, efficient method for the quantitative determination of physalin 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-C₁₈ column (4.6 mm×150 mm, 3.5 μm) 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 (t_max) was 0.69 h and the mean maximum concentration (C_max) was 77.48 ng·mL^-1. The area under the curve (AUC_0→t) was 280.78 ng·h·mL^-1, its t_1/2 was 2.89 h. CONCLUSION This study provides the physalin L characteristics of pharmacokinetics in rats, whitch is good for researchers on Physalis Calyx Seu Fructus (especially physalin compounds) in-depth study of pharmacological activity and pharmacokinetics.