Simultaneous determination of antidementia drugs in human plasma: Procedure transfer from HPLC-MS to UPLC-MS/MS

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• 作者：Muriel Noetzli^a ; Nicolas Ansermot^a ; Maria Dobrinas^a ; Chin B. Eap^a ; ^b ; ^{chin.eap@chuv.ch}
• 关键词：UPLC&ndash ; MS/MS ; Donepezil ; Galantamine ; Rivastigmine ; Memantine
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2012
• 期刊代码：65_07317085
• 类别：ch
• 出版时间：May-June, 2012
• 卷：64-65
• 期：Complete
• 页码：16-25
• 文件大小：921 K

摘要

A previously developed high performance liquid chromatography mass spectrometry (HPLC-MS) procedure for the simultaneous determination of antidementia drugs, including donepezil, galantamine, memantine, rivastigmine and its metabolite NAP 226-90, was transferred to an ultra performance liquid chromatography system coupled to a tandem mass spectrometer (UPLC-MS/MS). The drugs and their internal standards ([²H₇]-donepezil, [¹³C,²H₃]-galantamine, [¹³C₂,²H₆]-memantine, [²H₆]-rivastigmine) were extracted from 250 渭L human plasma by protein precipitation with acetonitrile. Chromatographic separation was achieved on a reverse phase column (BEH C18 2.1 mm 脳 50 mm; 1.7 渭m) with a gradient elution of an ammonium acetate buffer at pH 9.3 and acetonitrile at a flow rate of 0.4 mL/min and an overall run time of 4.5 min. The analytes were detected on a tandem quadrupole mass spectrometer operated in positive electrospray ionization mode, and quantification was performed using multiple reaction monitoring. The method was validated according to the recommendations of international guidelines over a calibration range of 1-300 ng/mL for donepezil, galantamine and memantine, and 0.2-50 ng/mL for rivastimgine and NAP 226-90. The trueness (86-108%), repeatability (0.8-8.3%), intermediate precision (2.3-10.9%) and selectivity of the method were found to be satisfactory. Matrix effects variability was inferior to 15%for the analytes and inferior to 5%after correction by internal standards. A method comparison was performed with patients鈥?samples showing similar results between the HPLC-MS and UPLC-MS/MS procedures. Thus, this validated UPLC-MS/MS method allows to reduce the required amount of plasma, to use a simplified sample preparation, and to obtain a higher sensitivity and specificity with a much shortened run-time.