HPLC-电喷雾串联质谱法快速测定人血浆中喹硫平的浓度

Rapid Determination of Plasma Concentration of Quetiapine by HPLC-ESI-MS/MS

目的：建立测定人血浆中喹硫平浓度的高效液相色谱-电喷雾串联质谱法。方法：血浆样品经醋酸乙酯-二氯甲烷（4：1）提取后测定，色谱柱为C18，流动相为甲醇-5mmol·L。甲酸铵（90：10），流速为1mL·min^-1，柱温为25℃。其中，样品经电喷雾离子源正离子化后，通过三重四极杆串联质谱仪，采用选择反应监测（SRM）对喹硫平（m／z384．3→253．1）和内标拉莫三嗪（m／z256→145）进行测定。并用此法测定34例精神分裂症患者稳态血药浓度。结果：血浆喹硫平检测浓度在2．5～500μg·L^-1范围内线·洼关系良好；分析方法的最低定量限为2．5μg·L^-1.喹硫平高、中、低3种浓度（250、100、5μg·L^-1）的平均回收率分别为101．03％、104．21％、97．74％，日内（n=5）、日间（n=3）RSD均小于15％。结论：本方法简便、快速、准确、灵敏、重现性好，可用于临床常规喹硫平血药浓度监测和药动学研究。

OBJECTIVE ： To establish a LC- ESI - MS/MS method for the determination of plasma concentration of quetiapine.METHODS：Quetiapine was extracted with ethyl acetate- dichiloromethane（4 ： 1）.The residues were analyzed with a LC-ESI- MS/ MS system（Dikma diamonsilTM Cl8 column） with the mobile phase consisted of methanol -5mmol ·L^ 1 ammonium formate（90 ： 10） at a flow rate of 1mL · min^-1.The column temperature was 25℃ .An agilent 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 384.3→25301 and m/z 256→145 was performed to detect quetiapine and the internal standard, respectively.The same method was used to determine the steady plasmadrug concentration in 34 schizophrenic patients .RESULTS：The calibration curves for quetiapine had good linearity over the range of 2.5--500μg · L^- 1.The limit of quantitation for quetiapine was 2.5μg · L^-1.The average recoveries for quetiapine（250,100,5μg · L^ -1） were 101.03 %, 104.21% and 97.74%, respectively.Both the within - day RSD （ n = 5） and between - day RSD （ n = 3） were less than 15 % .CONCLUSION ： The method provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring of quetiapine plasma and its phamacokinetic studies.