HPLC-电喷雾串联质谱法快速测定人血浆中喹硫平的浓度

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-1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范围内线性关系良好;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。

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

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 C18 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→253.1 and m/z 256→145 was performed to detect quetiapine and the internal standard,respectively.The same method was used to determine the steady plasma-drug 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.