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目的建立快速测定人血浆中奥氮平浓度的高效液相色谱串联质谱电喷雾检测法(LC-ESI-MS/MS)。方法以Dikma diamonsilTMC18反相柱(4.6mm×150mm,5μm)为色谱柱,流动相为甲醇-5mmol·L-1甲酸铵(90∶10),流速为1mL·min-1,柱温:25℃,以乙酸乙酯-二氯甲烷(4∶1)为提取剂。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择反应监测(SRM)对奥氮平(m/z313→256)和内标替米沙坦(m/z515.3→497.3)进行测定,并用此法测定36例患者稳态血药浓度。结果奥氮平的高(50μg·L-1)、中(25μg·L-1)、低(1μg·L-1)3个浓度的平均回收率分别为100.14%、100.33%和100.21%,日内(n=5)、日间(n=3)RSD均小于15%;分析方法的最低定量限为0.5μg·L-1。线性范围为:0.5～100μg·L-1,回归方程为F=1.5295ρ-0.0143,r=0.999(n=8),权重系数为1/ρ。结论该方法灵敏、准确、简单、快速,可用于临床血浓监测和药动学研究。
OBJECTIVE To establish a high performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS / MS) method for the rapid determination of olanzapine in human plasma. Methods The mobile phase was methanol-5mmol·L-1 ammonium formate (90:10) with a flow rate of 1mL · min-1 on a Dikma diamonsil TMC18 reverse phase column (4.6mm × 150mm, 5μm) , With ethyl acetate - dichloromethane (4: 1) as extractant. The samples were ionized by electrospray ionization and analyzed by selective quadrupole quadrupole mass spectrometry using selective reaction monitoring (SRM) for olanzapine (m / z 313 → 256) and internal standard telmisartan (m / z 515). 3 → 497.3) were measured, and using this method for determination of 36 patients with steady-state plasma concentration. Results The average recoveries of olanzapine at the concentrations of 50μg · L-1, 25μg · L-1 and 1μg · L-1 were 100.14%, 100.33% and 100.21% (n = 5), daytime (n = 3) RSD were less than 15%, and the lowest limit of quantitation was 0.5μg · L-1. The linear range was 0.5 ~ 100μg · L-1, the regression equation was F = 1.5295ρ-0.0143, r = 0.999 (n = 8), and the weight coefficient was 1 / ρ. Conclusion The method is sensitive, accurate, simple and rapid and can be used in clinical blood concentration monitoring and pharmacokinetic studies.