用液相色谱-质谱-质谱法测定人血清中非洛地平浓度

Quantitative determination of felodipine in human serum by LC-MS-MS method

目的:建立液相色谱-质谱-质谱(LC-MS-MS)法测定人血清中非洛地平的浓度。方法:血清样品经液-液萃取预处理。色谱柱为Xterra柱(50 mm×2.1 mm,3.5μm),流动相为乙腈-0.02%氨水,采用梯度洗脱,流速为0.3 mL/min。非洛地平和尼莫地平(内标)的多反应监测(MRM)扫描离子对分别为m/z382.1→145和m/z417.2→92,两者的保留时间分别为1.24 min和1.06 min。结果:非洛地平在0.04～20 ng/mL范围内线性关系良好(r=0.999 7),低、中、高浓度(0.08、8.0、16.0 ng/mL)的日内RSD分别为6.60%、7.22%和5.01%(n=6),日间RSD分别为9.42%、8.46%和5.12%(n=14),准确度为98.21%～106.20%(n=6)。结论:本法操作简便,检测准确、灵敏、专一,重复性好,适用于非洛地平血药浓度监测和药动学及生物利用度研究。

Objective： To establish a LC-MS-MS method for determining the concentration of felodipine in human serum. Methods：The serum samples were pretreated by liquid-liquid extraction. The chromatographic column was a Xterra column （50 mm×2.1 mm, 3.5 μm）. The mobile phase consisting of acetonitrile-0.02% ammonia water was eluted at a flow rate of 0.3 mL/min with gradient program. Felodipine and its internal standard nimodipine was monitored in multiple reaction monitoring（MRM） mode. The fragmentation transitions from precursor to production were m/z 382. 1/145 for felodipine and m/z 417.2/92 for nimodipine. The retention time of felodipine and nimodipine was 1.24 and 1.06 min, respectively. Results： For felodipine, the linear range was 0.04-20 ng/mL （r= 0. 999 7）. At low, middle and high concentrations（0.08,8.0,16.0 ng/mL）, the intra-day RSDs were 6. 60%,7. 22% and 5.01% （n=6） ,the inter-day RSDs were 9. 42%,8. 46% and 5. 12%（n= 14） ,and the accuracy rates were 98.2%- 106.20%（ n = 6 ）. Conclusion： This method is simple, accurate, sensitive, specific and reproducible for the determination of felodipine in human serum. It is suitable for therapeutic drug monitoring,pharmacokinetic and bioavailability study of felodipine.