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DOI: 10.1055/s-0031-1296631
Determination of Paroxetine in Plasma by Liquid Chromatography Coupled to Tandem Mass Spectrometry for Pharmacokinetic and Bio equivalence Studies
Publication History
Publication Date:
21 December 2011 (online)
Abstract
A rapid and validated liquid chromatography coupled to tandem mass spectro-metric 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, m/z 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.