Objective:To develop a sensitive HPLC-MS/MS method for analyzing donepoezil and its active metabolite 6-O-desmethyl donepezil in human plasma. Methods: Donepoezil and 6-O-desmethyl donepezil in plasma samples were extracted with dichloromethane after addition of internal standard. The analytes went through Shis-heido C18 column (100mm ×4.6mm,5 μm) with mobile phase methanol-(5 mmol·L-1) ammonium acetate-formic acid (80:20:0.05) ;the flow rate was 0.2 mL·min-1 ;the column temperature was ambient temperature ;ESI + was performed with MRM mode. Results:The calibration curves of donepoezil and 6-O-desmethyl donepezil were linear in the ranges of 0. 05 -15 ng·mL-1 and 0. 008 ~ 2.4 ng·mL-1 . The LLOQs of donepoezil and 6-O-desmethyl donepezil in plasma were 0.05 and 0. 008 ng·mL-1 , respectively. Both the intra- and inter-day RSDs were less than 9% and the relative recovery was 96% ~ 103% . The concentration change of the samples in stability assay was within ±15%. Conclusion: The method is simple and sensitive with good recovery and can be used in analyzing donepoezil and 6-O-desmethyl donepezil in plasma samples.%目的:建立HPLC-MS/MS法测定血浆中多奈哌齐及其代谢物6-O-去甲基多奈哌齐浓度.方法:采用HPLC-MS/MS法,加入内标后,样品用二氯甲烷为萃取剂提取后进样,以Shisheido C18(100 mm ×4.6mm,5μm)为色谱柱,甲醇-5 mmol·L -1醋酸铵-甲酸(80∶20∶0.05)为流动相,流速为0.2 mL· min -1,柱温为室温.离子化方式为电喷雾离子化,多反应离子监测.结果:多奈哌齐及6-O-去甲基多奈哌齐标准曲线线性范围分别为0.05～15 ng·mL-1和0.008～2.4 ng· mL -1,定量下限分别为0.05和0.008 ng·mL-1,二者日内RSD及日间RSD均＜9％,方法回收率在96％～103％之间.稳定性考察试验,二者血药浓度变化率均在±15％内.结论:该方法简单,快速,可满足多奈哌齐及6-O-去甲基多奈哌齐血药浓度的测定及多奈哌齐药代动力学研究.
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