目的建立同时测定人血浆中苯海拉明、氯苯那敏、异丙嗪、氯雷他定、非索非那定、地氯雷他定、左西替利嗪、赛庚啶浓度的超高效液相色谱质谱(UPLC-MS/MS)法。方法以盐酸吡格列酮为内标,血浆经甲醇直接沉淀后进样分析,用UPLC-MS/MS法进行检测。色谱柱为ACQUITY UPLC HSS C18柱,流动相为含0.01%甲酸的水溶液-0.01%甲酸的甲醇溶液,流速为0.3 mL·min 230001,China,电喷雾离子源,用多反应监测,正离子分段扫描分析。结果苯海拉明、氯苯那敏、异丙嗪、氯雷他定、非索非那定、地氯雷他定、左西替利嗪、赛庚啶血药浓度分别在1.15×10^-3-2.30×10^-1,2.48×10^-4-2.48×10^-2,2.86×10^-3-2.86×10^-1,2.50×10^-4-2.50×10^-2,5.50×10^-3-2.20,2.20×10^-4-2.20×10^-2,5.70×10^-3-2.28,3.50×10^-3-3.50×10^-1μg·m L^-1线性关系良好;最低定量下限分别为1.15×10^-3,2.48×10^-4,2.86×10^-3,2.50×10^-4,5.50×10^-3,2.20×10^-4,5.70×10^-3,3.50×10^-3μg·m L^-1。日内、日间精密度RSD均〈15%;提取回收率均〉65%,RSD均〈15%。结论该方法灵敏、快速、准确、专属性强,可用于上述8种抗组胺类药物的血药浓度监测及药代动力学研究。
Objective To develop the method for simultaneous determi- nation of diphenhydramine, chlorpheniramine, proazamine, loratadine, fexofenadine, desloratadine, levocetirizine and eyproheptadine in human plasma. Methods UPLC -MS/MS was adopted to analyze plasma with protein precipitated by methanol. Pioglitazone hydrochloride was as internal standard. Plasma samples were separated on ACQUITY UPLC HSS C18 column with aqueous solution (0. 01% formic acid) - methanol (0.01% formic acid) as mobile phase, and at a flow rate of 0. 3 mL·min^-1 Multiple reaction monitoring ( MRM ) mode was performed combined with the positive ion mode for quantification in three sections. Results The liner calibration curve of 8 antihistamine drugs were obtained in the concentration range of 1.15 × 10^-3 - 2.30 × 10^-1, 2. 48 × 10^-4 -2. 48 × 10^-2, 2.86 × 10^-3 -2. 86 × 10^-1 , 2. 50 × 10^-4 -2. 50 × 10^-2, 5.50 × 10^-3 -2. 20, 2. 20 × 10^-4 - 2.20 × 10^-2, 5.70 × 10^-3 - 2. 28and 3.50 × 10^-3 - 3.50 × 10^-1 μg·mL^-1, respectively. The lowest detection limit were 1.15 × 10^-3, 2. 48 × 10^-4, 2. 86 × 10^-3, 2. 50 × 10^-4, 5.50 × 10^-3, 2. 20 × 10^-4, 5.70× 10^-3, 3.50 × 10^-3μg·mL^-1, respectively. The RSD of inter- day and intra -day were less than 15%. The relative recovery was more than 65%, and the RSD were less than 15% . Conclusion The method is accurate, sensitive and suitable for determination of these 8 antihistamine drugs in human plasma.