title: ESI-MS/MS stability-indicating bioanalytical method development and validation for simultaneous estimation of donepezil, 5-desmethyl donepezil and 6-desmethyl donepezil in human plasma.
abstract: A bioanalytical method was developed and validated to estimate donepezil, 6-desmethyl donepezil and 5-desmethyl donepezil simultaneously in human plasma using galantamine as an internal standard (IS). The chromatographic separation was achieved on a reverse-phase XTerra RP (150 × 4.6 mm, 5 µm) column without affecting recovery (mean recovery > 60% with CV < 10%) for all analytes. ESI-MS/MS multiple reaction monitoring in positive polarity was used to detect mass pairs for donepezil (m/z 380.3 → 91.3), 6-desmethyl donepezil (m/z 366.4 → 91.3), 5-desmethyl donepezil (m/z 366.4 → 91.3) and galantamine m/z (288.1 → 213.0). The linearity was established over a dynamic range of 0.339-51.870, 0.100-15.380 and 0.103-15.763 ng/mL for donepezil, 6-desmethyl donepezil and 5-desmethyl donepezil, respectively. The current method shows that minimal conversion of labile metabolites to parent donepezil in plasma as stability was successfully achieved for 211 days at -15 °C storage temperature. The method was successfully applied to a clinical study after administration of 10 mg donepezil tablets to healthy male Indian volunteers.
authors: Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd, GP-5, HSIDC, Sector-18, Udyog Vihar Industrial Area, Old Delhi Gurgaon Road, Gurgaon 122015, Haryana, India.
authors: Arshad H
authors: AH
authors: Khuroo
authors: Sanjay J
authors: SJ
authors: Gurule
authors: Tausif
authors: T
authors: Monif
authors: Dipanjan
authors: D
authors: Goswami
authors: Arabinda
authors: A
authors: Saha
authors: Santosh K
authors: SK
authors: Singh
mesh_terms: D019540:Area Under Curve; D002853:Chromatography, Liquid; D000077265:Donepezil; D004355:Drug Stability; D006801:Humans; D007189:Indans / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C574332:5-desmethyl donepezil; C534900:6-O-desmethyl donepezil; D007189:Indans; D010880:Piperidines; D000077265:Donepezil