建立人血浆中拉呋替丁的液相色谱质谱联用测定方法

Determination of lafutidine in human plasma by HPLC-MS

目的建立人血浆中拉呋替丁(制胃酸药)的LC-MS测定方法。方法采用单剂量单周期給药试验设计,12名健康受试者服用拉呋替丁片10mg后,测定了不同时间内的血药浓度。在血浆0.5mL中加入内标盐酸雷诺嗪10μL碱化,以乙醚5mL提取,进行LC-MS法检测。流动相由0.02%甲酸与0.5mmol.L-1醋酸铵的水溶液和甲醇组成,流量为0.2mL.min-1;色谱柱为Shim-PackODS(5μm,150mm×2.0mm),质谱采用选择性离子检测方法。结果拉呋替丁的线性范围为1.0～400.0μg.L-1,最低检测浓度为1.0μg.L-1,批间和批内的变异系数均<10%。结论该法简便、准确、灵敏度高。

Objective To establish a high -performance liquid chroma- tography- mass spectrometry （HPLC -MS ） method for determination of lafutidine concentration in human plasma. Methods Twelve healthy volunteers were taken a single dose of 10 mg lafutidine and drug concentrations in the plasma were measured by the HPLC - MS method. Ten μL of ranolazine hydrochloride （2.0 μg · mL ^-1 , internal standard） was added to 0.5 mL of plasma. The plasma samples were extracted with 5 mL ether. The residue was dissolved in carbinol and 2 μL was injected into an ODS （5 μm,150 mm ×2.0 mm） column. The mobile phase consisted of carbinol at flow rate of 0.2 mL · min^ -1. The eluate from the HPLC column was plumbed dire-ctlyinto ESI probe. Analysis in the mass spectrometer was operated in the selection monitoring model. Results The standard curve was linear in the rang of 1 -400 μg · L^-1. The detection limit was 1.0 μg · L^-1. The inter - day, intra - day variability and relative recovery rate were suitable for biological analysis. Conclusion The method of HPLC - MS is suitable for pharmacokinetic study of lafutidine in human plasma.