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目的建立超高效液相色谱-串联质谱法测定大鼠血浆中淫羊藿素(ICT)浓度,并用于研究大鼠静脉注射ICT的药动学。方法采用乙腈提取血浆中ICT,以香豆雌酚(CMT)为内标,在BEH C18色谱柱(2.1 mm×50 mm,1.7μm)上以流动相乙腈-水-甲酸铵-甲酸梯度洗脱,流速0.3 ml/min,柱温40℃,分析时间6.5 min;在电喷雾离子化电离源上以多反应监测方式进行负离子检测,用于定量分析的离子反应分别为m/z 367.1→297.1(ICT)和m/z 267.0→211.1(CMT)。大鼠静脉注射10 mg/kg ICT,采集不同时刻血样并测定药物浓度。结果 ICT的线性范围为0.5~20 ng/ml,方法定量下限为0.5 ng/ml。ICT日内和日间精密度(RSD)在8.1%以内,准确度在95.3%~99.3%,提取回收率为90.1%~92.1%,基质效应为97.5%~101.2%。大鼠静脉注射ICT的t1/2为(1.13±0.32)h,表观分布容积为(4.54±0.27)L/kg,清除率为(2.91±0.68)L/(h·kg)。结论该方法速度快、专属性好、准确度高,适用于ICT临床前药动学研究。
Objective To establish an ultra high performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) method for the determination of icaritin (ICT) in rat plasma and to study the pharmacokinetics of intravenous ICT in rats. Methods The plasma ICT was extracted by acetonitrile. The coumarin (CMT) was used as the internal standard and eluted with a mobile phase of acetonitrile - water - ammonium formate - formic acid gradient on a BEH C18 column (2.1 mm × 50 mm, 1.7 μm) , The flow rate was 0.3 ml / min, the column temperature was 40 ℃, and the analysis time was 6.5 min. Negative ion detection was performed on the electrospray ionization ionization source by multiple reaction monitoring. The ion reactions for quantitative analysis were m / z 367.1 → 297.1 ICT) and m / z 267.0 → 211.1 (CMT). Rats were intravenously injected with 10 mg / kg ICT, blood samples were taken at different times and drug concentrations were determined. Results The linear range of ICT was 0.5-20 ng / ml, and the limit of quantification was 0.5 ng / ml. Intra-day and inter-day ICT precision was within 8.1%, accuracy was 95.3% -99.3%, extraction recovery was 90.1% -92.1%, matrix effect was 97.5% -101.2%. The t1 / 2 of intravenous injection of ICT in rats was (1.13 ± 0.32) h, the apparent volume of distribution was (4.54 ± 0.27) L / kg and the clearance rate was (2.91 ± 0.68) L / (h · kg). Conclusion The method is rapid, specific and accurate, suitable for preclinical pharmacokinetic studies of ICT.