【摘要】 目的研究大鼠分别灌胃和静脉给药芹黄春(芹菜素-7-O-β-D吡喃葡萄糖苷)溶液后,血浆中的芹黄春药物浓度及其药代动力学性质。方法 6只雌性Sprague Dawley大鼠随机分为两组,每组3只,分别经灌胃(10 mg/kg)和静脉注射(2 mg/kg)给予芹黄春溶液后,按设计的时间点从大鼠眼内眦静脉丛采集血液样品,置于肝素化的离心管中,低温离心得血浆。采用甲醇沉淀法处理血浆生物样品,利用LC-MS/MS方法对血浆生物样品进行分析。药代动力学参数由Kinetica 2000软件进行计算。结果芹黄春浓度在1~2 000 ng/mL范围内线性关系良好(r=0.997 4),定量下限为1 ng/mL,低(8 ng/mL)、中(100 ng/mL)、高(1 200 ng/mL)3个浓度的提取回收率均大于90%,日内日间精密度和稳定性的RSD均小于12.8%,日内日间准确度在91.5%~107%,方法学考察均符合要求。大鼠经静脉注射和灌胃芹黄春后,Cmax分别为(2 363±96)ng/mL和(13.3±5.8)ng/mL,AUC0~∞分别为(796±201)h·ng/mL和(28.9±9.2)h·ng/mL,大鼠经静脉注射和后t1/2为(1.20±0.17)h,芹黄春的口服生物利用度约为0.6%。结论所建立的LC-MS/MS分析方法方便、快速,灵敏度高,准确度好,可用于大鼠血浆芹黄春浓度测定及其药代动力学的研究。更多还原

【Abstract】 Objective To quantify apigetrin in rat plasma by LC-MS/MS, and investigate pharmacokinetic properties of apigetrin after oral or intravenous administration of apigetrin solution to rats. Methods Six female Sprague Dawley rats were randomly divided into two groups, with three rats in each group, to receive a single intravenous dose(2 mg/kg) or an oral dose of apigetrin solution(10 mg/kg). Serial blood samples were collected from the orbital sinus under light ether anesthesia. Each plasma sample was precipitated with the IS-spiked methanol solution.The mixture was well followed by a vortex shake for 5 min and centrifuged at 13 000 r/min for 10 min. The resulting supernatant was directly applied for LC-MS/MS analysis. Pharmacokinetic parameters were determined with Kinetica 2000 software. Results Good linearity was found in the range of 1~2 000 ng/mL for apigetrin. The lower limit determination of apigetrin was 1 ng/mL. The relative extraction recoveries were higher than 90% at three concentrations(8 ng/mL, 100 ng/mL, 1 200 ng/mL). The RSD values for stability of intraday and interday precision were always less than 12.8%. Intraday and interday accuracy ranged from 91.5% to 107%. The accuracy, precision, stability, extraction recoveries and linearity were found to be within the acceptable criteria. This method was successfully applied to a pharmacokinetic study after oral or intravenous administration of apigetrin solution to rats. The Cmaxwas(2 363±96) ng/mL and(13.3±5.8) ng/mL respectively. The AUC0~∞was respectively(796±201) h· ng/mL and(28.9±9.2) h· ng/mL. The plasma t1/2after apigetrin through intravenous administration was(1.20±0.17) hour and its oral bioavailability was very low(0.6%). Conclusion The LC-MS/MS method for measurement of apigetrin was developed and validated, which can be successfully applied in determination of apigetrin in rat plasma and pharmacokinetics study.更多还原