title: Liquid chromatography tandem mass spectrometry method for the simultaneous stereoselective determination of venlafaxine and its major metabolite, O-desmethylvenlafaxine, in human plasma.
abstract: A sensitive, accurate and highly stereoselective assay for the simultaneous determination of venlafaxine (VEN) and its equipotent metabolite, O-desmethyl venlafaxine (ODV), in human plasma was developed and validated. Analytes were simultaneously extracted from plasma using solid-phase extraction and detected by tandem mass spectrometry in positive ion mode with a turbo ion spray interface. Deuterium-labeled VEN and ODV were used as internal standards. Chromatographic separation was performed on a Chiral AGP column, using a time programmed gradient flow with a total run time of 16 min. The method has a lower limit of quantitation of 0.60 ng/mL. The assay was linear over a range 0.60-300.00 ng/mL for both the enantiomers of VEN and ODV, respectively, with coefficient of correlation > 0.99. The extraction recoveries were >77.0% on an average for all the four analytes. The analytes were found stable in plasma through three freeze (-15 °C) and thaw cycles and under storage at room temperature for 8 h, and also in mobile phase at 10 °C for 54 h. The method has shown good reproducibility, with intra- and inter-day variation coefficients < 9%, for all the analytes, and has proved to be very reliable for analysis of VEN and its metabolite in clinical study samples.
authors.affiliation: Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Limited, Plot no. GP-5, Sec. 18, HSIDC, Old Delhi-Gurgaon Road, Gurgaon-122015, Haryana, India. lalit.dutta@ranbaxy.com
authors.forename: Lalit
authors.initials: L
authors.lastname: Dutta
authors.forename: Syed Imran
authors.initials: SI
authors.lastname: Ahmad
authors.forename: Subhra Kanti
authors.initials: SK
authors.lastname: Mukherjee
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mishra
authors.forename: Arshad
authors.initials: A
authors.lastname: Khuroo
authors.forename: Tausif
authors.initials: T
authors.lastname: Monif
mesh_terms: D000085:Acetates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003511:Cyclohexanols / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000069468:Desvenlafaxine Succinate; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016018:Least-Squares Analysis; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D000069470:Venlafaxine Hydrochloride
chemical_list: D000085:Acetates; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; C018824:ammonium acetate; D000069468:Desvenlafaxine Succinate