超高效液相色谱-质谱联用法检测人全血中氯喹、羟氯喹、阿比多尔及其临床应用

Determination of chloroquine,hydroxychloroquine and arbidol in human whole blood by UPLC-MS/MS and its clinical applications

目的:建立并验证一种人全血中氯喹、羟氯喹、阿比多尔的检测方法,并将其用于临床检测。方法:全血样本经氯化铵裂解和乙腈蛋白沉淀后,采用液相-串联质谱联用仪测定。色谱柱为BEH C_(18),以含0.5%甲酸乙腈溶液-0.5%甲酸水溶液为流动相梯度洗脱,流速为0.4 mL·min^(-1),电喷雾正离子模式,多反应监测。结果:氯喹、羟氯喹、阿比多尔在8~1600 ng·mL^(-1)线性关系良好;批内和批间精密度(RSD)均在12.71%以内,批内和批间准确度(RE)均在-7.12%~13.51%;提取回收率均在76.50%~92.49%;内标归一化的基质因子变异系数(RSD)均小于15%;在多种储存条件下,处理前后的样品稳定性良好。结论:该方法专属性强,准确度高,重复性好,可用于3种药物治疗药物监测及中毒检测。

OBJECTIVE To develop and validate a method for the determination of chloroquine,hydroxychloroquine and arbidol in human whole blood for clinical use.METHODS Whole blood samples were lysed by ammonium chloride and precipitated by acetonitrile,and then determined by liquid chromatography-mass spectrometry.The chromatographic column was BEH C_(18),with a mobile phase gradient elution of acetonitrile solution containing 0.5%formic acid and aqueous solution containing 0.5%formic acid at a flow rate of 0.4 mL·min^(-1).Electrospray positive ion mode and multiple reaction monitoring were used.RESULTS Chloroquine,hydroxychloroquine and arbidol had good linearity at 8-1600 ng·mL^(-1).Intra-and inter-batch precision(RSD)were within 12.71%,and intra-and inter-batch accuracy(RE)ranged from-7.12%to 13.51%.The extraction recovery ranged from76.50%to 92.49%.Internal standard normalised coefficient of variation(RSD)for matrix factor were less than 15%.The samples before and after treatment were stable under various storage conditions.CONCLUSION The method is specific,accurate and reproducible,which can be used for therapeutic drug monitoring and poisoning detection of three kinds of drug therapy.