LC-MS/MS法测定人血浆中的非洛地平浓度

Determination of Felodipine in Human Plasma by LC-MS/MS

目的:建立高效液相色谱串联质谱法(LC-MS/MS)测定人血浆中的非洛地平浓度。方法:以非洛地平-d3为内标,血浆样品采用乙腈进行蛋白质沉淀前处理后,采用Waters Xbridge-C18(2.1 mm×50 mm,3.5μm),以水/甲酸/1 mol·L^(-1)醋酸铵(100/0.2/0.1,v/v/v)、乙腈/甲酸/1 mol·L^(-1)醋酸铵(100/0.2/0.1,v/v/v)为A、B流动相,梯度洗脱;使用电喷雾离子源(ESI),正离子多反应监测(MRM)模式检测,非洛地平和内标的检测离子对分别为m/z 384.2→352.0和m/z 387.2→351.9。结果:非洛地平在0.02~4 ng·mL^(-1)范围内线性关系良好,最低定量限为0.02 moL·L^(-1),分析物在血浆中的提取回收率在81.1%~107.3%,准确度在±15%之内,批内、批间精密度均<10%,无明显基质效应影响和残留效应。结论:本方法准确快速,灵敏度高,专属性强,适用于本品的血药浓度检测。

Objective:To establish a rapid and sensitive LC-MS/MS method for the quantification of felodipine in human plasma.Methods:This method selected felodipine-d3 as an internal standard.After protein precipitation by acetonitrile,felodipine and felodipine-d3 were separated on a Waters Xbridge-C18(2.1 mm×50 mm,3.5μm)column using water/formic acid(FA)/1 mol·L^(-1)ammonium acetate(100/0.2/0.1,v/v/v)-acetonitrile/FA/1 mol·L^(-1)ammonium acetate(100/0.2/0.1,v/v/v)as mobile phase A and B in a gradient mode.A multiple reaction monitoring mode(MRM)using positive ion,electrospray ionization(ESI+)was used for the detection of m/z 384.2→352.0(felodipine)and m/z 387.2→351.9(felodipine-d3).Results:The liner range was from 0.02 to 4 ng·mL^(-1)for felodipine in human plasma and the quantification limit was 0.02 ng·mL^(-1).The intra-run and inter-run mean relative errors were within 15%,and the within-run and between-run precisions were within 10%.There was no obvious matrix or carryover effect,and good selectivity was obtained in this method.Conclusions:The method was rapid,sensitive and suitable for the detection of felodipine concentrations in human plasma.