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目的 建立测定人血浆中卢帕他定浓度的LC-ESI-MS/MS方法.方法 血浆样品加入内标,碱化后用二氯甲烷:乙酸乙酯(20:80)提取,在37℃真空干燥箱中干燥至干,残渣用200 μL流动相溶解后进样.色谱条件为:色谱柱为Agilent Eclipse XDB-C18(4.6 mm×150 mm,5 μm);流动相为乙腈(含1%甲酸):20 mmol·L-1醋酸铵(76:24,V/V),流速为0.6 mL·min-1.质谱条件:采用美国安捷仑1100高效液相色谱系统和离子阱(Agilent MSD Trap XCT)检测仪,质谱条件为电喷雾离子源,检测方式为正离子电离、多离子反应监测(MRM),用于定量分析的离子为卢帕他定m/z 416→309,内标氯雷他定m/z 383→337.结果 该方法应用于检测20名健康志愿者服药后的血浆样品.线性范围为0.05～14 ngmL-1(r=0.998),日内和日间精密度均低于15%,方法回收率为85.1%～114.0%.最低检测限为0.05 ng·mL-1(当n=5时,RSD=9.22%).结论 该方法灵敏、准确、快速,可用于该药药代动力学和生物等效性研究.“,”Aim To develop and validate a sensitive and specific liquid chromatography electrospray ionization ion-trap mass spectrometry (LC-ESI-MS/MS) method for the identification and concentration of rupatadine in human plasma. Methods After the addition of the internal standard (IS, loratadine) and 0.01 mol·L-1 sodium hydroxide solution, plasma samples were extracted with methylene chloride: ethyl acetate mixture (20:80, V/V). The organic layer was evaporated under vacuum drying at 37℃. The residue was reconstituted with 200 μL mobile phase. Chromatography was performed on an Agilent Eclipse XDB-C18 (4.6 mm × 150 mm, 5 μm) column with a mobile phase consisting of acetonitrile (1% formic acid) -20 mmol·L-1 ammonium acetate (76:24, V/V) at a flow-rate of 0.6 mL·min-1. Detection was performed on Agilent MSD Trap XCT ion-trap mass spectrometry connected to a Agilent 1100 high performance liquid chromatography (HPLC) by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) source. Rupatadine (MRM m/z 416 → 309) and loratadine (MRM m/z 383→ 337) were detected by Agilent MSD Trap XCT ion-trap mass analyser. Results The method was proved to be sensitive and specific by testing 20 different plasma batches. Linearity was established for the range of concentrations 0.05 - 14.0 ng·mL-1 with a coefficient of determination (r) of 0.998. The intra-and inter-day precision (RSD %) were lower than 15% and accuracy ranged from 85.1% to 114.0%. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.05 ng·mL -1 with a precision of 9.22% (n =5). Conclusion The proposed method is sensitive and reproducible enough to be used in pharmacokinetic, bioavailability or bioequivalence studies of rupatadine.