title: Quantitative determination of duloxetine and its metabolite in rat plasma by HPLC-MS/MS.
abstract: The major metabolite of duloxetine is a glucuronide conjugate of 4-hydroxy duloxetine (4-HD). However, interestingly, there have been no reports determining concentrations of 4-HD and no fully validated method has been established for measuring duloxetine and 4-HD in rat plasma. We developed a method for the simultaneous quantification of duloxetine and its metabolite in rat plasma using high-performance liquid chromatography tandem mass spectrometry. Duloxetine and 4-HD were analyzed on a reverse-phase C18 analytical column after protein precipitation of the plasma sample with methanol, using carbamazepine as an internal standard. The isocratic mobile phase of 5 mm ammonium acetate-methanol (4:6, v/v) was eluted at 0.4 mL/min. Quantification was performed on a triple-quadrupole mass spectrometer using electrospray ionization, and the ion transition monitored in selective reaction monitoring mode. The coefficient of variation for assay precision was <18.0%, and the accuracy was 84.0-118.0%. This method was successfully used to measure the concentrations of duloxetine and its metabolite in plasma following the oral administration of a single 40 mg/kg dose in rats.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-woo
authors.initials: JW
authors.lastname: Chae
authors.forename: Hyun-moon
authors.initials: HM
authors.lastname: Baek
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Ho-il
authors.initials: HI
authors.lastname: Kang
authors.forename: Kwang-il
authors.initials: KI
authors.lastname: Kwon
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D000068736:Duloxetine Hydrochloride; D000432:Methanol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013876:Thiophenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000085:Acetates; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride; C018824:ammonium acetate; D000432:Methanol
keywords: 4-hydroxy duloxetine (4-HD); LC/MS/MS; duloxetine; rat plasma