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 diamonsil^TM C₁₈ 反相柱（ 4.6 mm × 150 mm ， 5 μm ）为色谱柱，流动相为甲醇 -5 mmol·L^-1 甲酸铵（ 90 ∶ 10 ），流速为 1 mL·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/z 313 → 256 ）和内标替米沙坦（ <> m/z 515.3 → 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（ 50 μg · L^-1 ）、中（ 25 μg · L^-1 ）、低（ 1 μg·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 0.5 μg · L^-1 。线性范围为： 0.5~100 μg · L^-1 ，回归方程为 <> F =1.529 5 <> ρ - 0.014 3 ， <> 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 develop a LC-ESI-MS/MS method for olanzapine assay in plasma. METHODS Olanzapine was extracted with hexane-isoamyl alcohol. The residues were analyzed with a LC-ESI-MS/MS system (Dikma DiamonsilTM C18 column , 4.6 mm×150 mm，5 μm) with the mobile phase consisted of methanol:water with 5 mmol·L-1 ammonium formate (90∶10). A Agilent 6 410 triple quad mass spectrometer system equipped with an electrospray ionization ion-trap source was used as the detector and operated in the positive ion mode. Selected reaction monitoring(SRM) using the precursor to product ion combinations of m/z 313→256 and m/z 515.3→497.3 was performed to detect olanzapine and the internal standard, respectively. The method was used to evaluate clinical application for 36 patients after multiple oral doses of olanzapine tablets. RESULTS The average recoveries for olanzapine were 100.14%, 100.33% and 100.21%，respectively. The within-day (n=5) and between-day (n=3) precision of variation was less than 15%. The calibration curves for olanzapine had good linearity (r=0.999, n=8) within the range of 0.5～100 μg·L-1 . The limits of quantitation for olanzapine was 0.5 μg·L-1 . CONCLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring of olanzapine plasma and its pharmacokinetic studies.