title: Determination of paroxetine in plasma by liquid chromatography coupled to tandem mass spectrometry for pharmacokinetic and bioequivalence studies.
abstract: A rapid and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS-MS) has been developed and applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a liquid-liquid extraction of paroxetine (CAS 61869-08-7) and fluoxetine (internal standard, CAS 54910-89-3) with ether/methyl chloride (7:3, v/v) and separated by LC equipped with C18 column using acetonitrile: 5 mmol/L ammonium formate (4:3, v/v) as mobile phase. Detection is carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved by MS-MS analysis, mlz 330.0-->192.0 and m/ z 310-->148 for paroxetine and fluoxetine, respectively. The method has a total run time of 1.5 min and was linear over a working range of 0.05-20 ng/mL and the lower limit of quantification was 0.05 ng/ mL. No endogenous compounds were found to interfere with the analysis. The inter-day and intra-day accuracy was in the ranges of 102.69-107.79% and 102.07-109.57%, respectively and precision of inter-day and intra-day expressed as relative standard deviation were 1.86-9.99% and 1.52-6.28%, respectively. The validation of this method on linearity, specificity, accuracy, precision as well as applicability to pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 72 h after oral administration of 20 mg of paroxetine in 24 healthy volunteers were found to be good performance.
authors.affiliation: Department of Practical Arts Education, Gongju National University of Education, Gongju, Chungnam, South Korea.
authors.forename: Ok Hwa
authors.initials: OH
authors.lastname: Jhee
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Seo
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Yong Cheol
authors.initials: YC
authors.lastname: Jeon
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Yeon
authors.initials: Y
authors.lastname: Hur
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Heon-Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Seo Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Ju Seop
authors.initials: JS
authors.lastname: Kang
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D006801:Humans; D017374:Paroxetine / Q000097:blood* / Q000493:pharmacokinetics*; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency