title: Development and validation of a sensitive UPLC-MS/MS method for the simultaneous determination of dapoxetine and its two metabolites in human plasma.
abstract: A sensitive and rapid ultra performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) method was developed to determine dapoxetine and its two major metabolites (dapoxetine-N-oxide and desmethyldapoxetine) in human plasma simultaneously. After a simple protein precipitation, the analytes and the combined internal standard (carbamazepine) were separated on an Acquity UPLC BEH C18 column using a mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution. Mass spectrometric analysis was performed using a XEVO TQD triple quadruple mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions are of m/z 306.3→261.2, m/z 322.2→261.2, m/z 292.2→261.2 and m/z 237.1→194.2 for dapoxetine, dapoxetine-N-oxide, desmethyldapoxetine and IS, respectively. The linearity of this method was found to be within the concentration range of 1.0-200ng/mL for dapoxetine; 0.5-100ng/mL for dapoxetine-N-oxide; and 0.1-5.0ng/mL for desmethyldapoxetine in human plasma, respectively. Only 4.0min was needed for an analytical run. Intra-day and inter-day accuracy and precision were within the acceptable limits of ±15% at all of the concentrations. This assay was successfully used to support a clinical pharmacokinetic study following oral administration of dapoxetine tablets in healthy Chinese subjects.
authors.affiliation: The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, PR China. Electronic address: lyzhangweimin@163.com.
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: Pharmaceutical College of Henan University, Kaifeng, Henan 475004, PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: Qiang
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang, Henan 471003, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ying-Fei
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang, Henan 471003, PR China.
authors.forename: Sun
authors.initials: S
authors.lastname: Ming
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang, Henan 471003, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D001596:Benzylamines / Q000097:blood* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D064368:Healthy Volunteers; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000097:blood* / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001596:Benzylamines; D009281:Naphthalenes; D017367:Selective Serotonin Reuptake Inhibitors; C522496:dapoxetine-N-oxide; C080599:mono-desmethyldapoxetine; C080598:dapoxetine
keywords: Dapoxetine; Human plasma; Metabolite; Pharmacokinetic; UPLC-MS/MS