UPLC-MS/MS测定大鼠血浆中紫花前胡素的血药浓度及其药动学研究

Study on Plasma Concentration and Pharmacokinetics of Decursin in Rat Plasma by UPLC-MS/MS

关键词:  超高效液相色谱-串联质谱法|紫花前胡素|药动学|大鼠

Key words:  UPLC-MS/MS|decursin|pharmacokinetics|rats

摘要:

目的 建立UPLC-MS/MS测定大鼠血浆中紫花前胡素的血药浓度，并用于口服和静脉注射后紫花前胡素的药动学特征研究。方法 大鼠血浆样本采用乙腈沉淀法去除蛋白。使用地西泮作为内标，UPLC BEH C₁₈柱（2.1 mm×50 mm，1.7 μm）为分离柱，以乙腈-0.1%甲酸为流动相，进行梯度洗脱，流速为0.4 mL·min^-1，分析时间为4.0 min。用电喷雾离子源（ESI），正离子检测，多反应监测方式进行定量分析，紫花前胡素m/z 329.0→229.0和内标m/z 285.1→193.3。结果 紫花前胡素在1~60 ng·mL^-1内线性关系良好，定量限为1 ng·mL^-1。日内、日间精密度RSD均<14%，准确度范围在88.5%~107.5%，回收率>93.3%，基质效应在89.3%~93.5%。结论 本方法具备灵敏、快速、选择性好的特点，可应用于紫花前胡素大鼠药动学研究。

Abstract:

OBJECTIVE To establish a method for plasma concentration of decursin in rat plasma by UPLC-MS/MS and apply to the pharmacokinetic characteristics of decursin after oral and intravenous injection. METHODS The protein of rat plasma was removed by acetonitrile precipitation method. Diazepam was used as internal standard. UPLC BEH C₁₈ column (2.1 mm×50 mm, 1.7 μm) was used as the separation column. Acetonitrile and 0.1% formic acid was used as a mobile phase by gradient elution. The flow rate was 0.4 mL·min^-1, the analysis time was 4.0 min. The quantitative analysis were detected by electrospray ionization(ESI), positive ion detection combined with multiple reaction monitoring mode. The following transitions were obtained at m/z 329.0→229.0 for decursin and m/z 285.1→193.3 for internal standard. RESULTS The linear relationship of decursin in 1-60 ng·mL^-1 was good and limit of quantitation was 1 ng·mL^-1. Intra-day and inter-day precisions were <14%, the accuracy range was between 88.5% and 107.5%, the recovery was >93.3%, and the matrix effect was between 89.3% and 93.5%. CONCLUSION The method is sensitive, fast, specific, and has been successfully applied to a pharmacokinetic study of decursin.