HPLC-ESI-MS测定人血浆中多奈哌齐的浓度

目的建立快速、灵敏的HPLC-MS检测方法测定人血浆中多奈哌齐浓度。方法以马来酸氯苯那敏为内标,待测血浆经碱化处理后,经乙酸乙酯进行液-液萃取,采用Shim-packODSC18柱（250mm×2.0mm,5μm）,以甲醇-0.1%醋酸溶液（60∶40）为流动相,流速0.2mL·min^-1,柱温35℃。采用质谱电喷雾离子源正源（ESI＋）将样品离子化,选择性离子监测（SIM）准分子离子峰。结果多奈哌齐在0.1～16.0ng·mL^-1内线性关系良好（r=0.9998）,最低定量限为0.1ng·mL^-1。方法回收率为92.5%～105.3%,提取回收率均大于75%,批内与批间RSD均小于10%。结论该方法简单,快速、灵敏度高、专属性强,适用于人血浆中多奈哌齐浓度的测定及药动学研究。

Determination of Donepezil in Human Plasma by HPLC-ESI-MS

OBJECTIVE To establish an HPLC-MS method for the determination of donepezil in human plasma. METHODS Alkalized plasma was extracted with ethyl acetate and chlorphenamine maleate was used as internal standard. Solutes were separated on a Shim-pack ODS C18 column（250 mm×2.0 mm, 5 μm）with a mobile phase of methanol-0.1%acetate buffer （60 ∶ 40）. The flow rate was 0.2 mL·min^-1 and column was used with temperature of 35 ℃ . Donepezil and internal standard were ionized in the eletrospray ionization （ESI） with positive source of the mass spectrometer and detected in selected ionization monitor （SIM） mode. RESULTS The calibration curve was linear in the range of 0.1-16.0 ng·mL^-1 （r=0.999 8） with the lower limit of quantitation, accuracy was within 92.5%-105.3%. The recovery of the extraction was more than 75%, intra- and inter-batch precision （RSD） were less than 10%. CONCLUSION The method is proved to be suitable for pharmacokinetics and determination of donepezil in human plasma with simple, quickness, sensitive and specificity.