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目的:建立灵敏、快速的亲水作用色谱-串联质谱法(HILIC-MS/MS)测定给予沙丁胺醇气雾剂后人血浆中的沙丁胺醇。方法:以d9-沙丁胺醇为内标,血浆样品经乙腈蛋白沉淀后,采用Luna HILIC(100 mm×3.0 mm,3μm)色谱柱分离。流动相为乙腈(含0.1%甲酸)-5 mmol.L-1醋酸铵溶液(氨水调节pH为8.5)(93∶7,v/v),等度洗脱,进样体积2.0μL,样品分析时间为3.5 min。采用电喷雾电离(ESI)源正离子模式、多反应监测(MRM),用于定量分析的离子反应分别为m/z 240→(148+166)(沙丁胺醇)和m/z 249→(149+167)(d9-沙丁胺醇)。结果:沙丁胺醇定量方法的线性范围为11.7～2340 pg.mL-1,定量下限达11.7 pg.mL-1,日内、日间精密度(RSD)均小于14.1%,准确度(RE)在-3.8%～-0.8%之间。本法成功应用于健康受试者给予硫酸沙丁胺醇气雾剂200μg后的药动学研究。结论:采用稳定同位素内标的HILIC-MS/MS法快速、灵敏和准确,适用于测定人血浆样品中的沙丁胺醇,可测定给药后24 h的血浆浓度。
OBJECTIVE: To establish a sensitive and rapid hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS / MS) for the determination of salbutamol in human plasma after salbutamol administration. Methods: D9-salbutamol was used as an internal standard. Plasma samples were precipitated with acetonitrile and separated on a Luna HILIC (100 mm × 3.0 mm, 3 μm) column. The mobile phase consisted of acetonitrile (containing 0.1% formic acid) and 5 mmol·L-1 ammonium acetate solution (ammonia water adjusted to pH 8.5) (93: 7, v / v) The time is 3.5 min. The ion reaction for ESI-ESI-MSMS and MRM was m / z 240 → (148 + 166) (salbutamol) and m / z 249 → (149+ 167) (d9-salbutamol). Results: The linear range of albuterol quantification was 11.7-2340 pg · mL-1 with a lower limit of quantitation of 11.7 pg · mL-1. The RSD was less than 14.1% and the accuracy (RE) was -3.8 % ~ -0.8% between. This method has been successfully applied to the pharmacokinetics of 200 μg salbutamol sulfate aerosol in healthy subjects. Conclusion: HILIC-MS / MS with stable isotope internal standard is rapid, sensitive and accurate and is suitable for the determination of albuterol in human plasma samples. The plasma concentration of 24 h after administration can be determined.