title: Simultaneous determination of antidementia drugs in human plasma: procedure transfer from HPLC-MS to UPLC-MS/MS.
abstract: 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 ([(2)H(7)]-donepezil, [(13)C,(2)H(3)]-galantamine, [(13)C(2),(2)H(6)]-memantine, [(2)H(6)]-rivastigmine) were extracted from 250 μL human plasma by protein precipitation with acetonitrile. Chromatographic separation was achieved on a reverse phase column (BEH C18 2.1 mm × 50 mm; 1.7 μm) 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' 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.
authors.affiliation: Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Hospital of Cery, Prilly, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Noetzli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ansermot
authors.forename: Maria
authors.initials: M
authors.lastname: Dobrinas
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D000077265:Donepezil; D004355:Drug Stability; D005702:Galantamine / Q000097:blood; D006801:Humans; D007189:Indans / Q000097:blood; D008559:Memantine / Q000097:blood; D018697:Nootropic Agents / Q000097:blood*; D010627:Phenethylamines / Q000097:blood; D010636:Phenols / Q000097:blood; D048448:Phenylcarbamates / Q000097:blood; D010880:Piperidines / Q000097:blood; D010949:Plasma / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D000068836:Rivastigmine; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: C494046:3-(1-dimethylaminoethyl)phenol; D007189:Indans; D018697:Nootropic Agents; D010627:Phenethylamines; D010636:Phenols; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine; D008559:Memantine