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Quantitative determination of paroxetine and its 4‐hydroxy‐3‐methoxy metabolite in plasma by high‐performance liquid chromatography/electrospray ion trap mass spectrometry: application to pharmacokinetic studies
Author(s) -
Segura Mireia,
Ortuño Jordi,
Farré Magí,
Pacifici Roberta,
Pichini Simona,
Joglar Jesús,
Segura Jordi,
Torre Rafael de la
Publication year - 2003
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1067
Subject(s) - chemistry , chromatography , metabolite , formic acid , selected reaction monitoring , electrospray ionization , high performance liquid chromatography , mass spectrometry , liquid chromatography–mass spectrometry , paroxetine , electrospray , ion trap , selected ion monitoring , tandem mass spectrometry , gas chromatography–mass spectrometry , biochemistry , receptor , serotonin
Abstract A high‐performance liquid chromatography (HPLC) method with tandem mass spectrometric detection is described for the determination of paroxetine, an antidepressant drug, and its metabolite (3 S ,4 R )‐4‐(4‐fluorophenyl)‐3‐(4‐hydroxy‐3‐methoxyphenoxymethyl)piperidine (HM paroxetine) in human plasma. Plasma samples were hydrolysed with hydrochloric acid and then analytes were extracted with ethyl acetate at alkaline pH. Extracts were analysed by HPLC coupled to an atmospheric pressure ionisation‐electrospray (ESI) interface and an ion trap mass spectrometer. Chromatography was performed on a reversed‐phase column using acetonitrile/0.02% formic acid (66:34, v/v) as a mobile phase. The mass spectrometer was operated in the multiple reaction monitoring mode. The method was validated over concentration ranges of 0.75–100 μg/L and 5–100 μg/L for paroxetine and HM paroxetine, respectively. Mean recoveries of 77% for paroxetine and 76% for HM paroxetine were found, with precision always better than 15%. The limits of detection and quantification were 0.20 and 0.70 μg/L for paroxetine, and 0.70 and 2.20 μg/L for its metabolite. The method was applied to the analysis of plasma samples obtained from nine healthy male volunteers administered with a single oral dose of 20 mg paroxetine. After the 20‐mg dose, the mean peak plasma concentration was 8.60 μg/L for paroxetine and 92.40 μg/L for HM paroxetine showing a tenfold ratio between the metabolite and the parent drug along the entire time‐concentration curve. Copyright © 2003 John Wiley & Sons, Ltd.