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Liquid chromatography/tandem mass spectrometry for the determination of fluoxetine and its main active metabolite norfluoxetine in human plasma with deuterated fluoxetine as internal standard
Author(s) -
Li Chuan,
Ji Zhouhua,
Nan Fajun,
Shao Qingxiang,
Liu Ping,
Dai Jieyu,
Zhen Jiang,
Yuan Hao,
Xu Fang,
Cui Jian,
Huang Bin,
Zhang Meiyun,
Yu Cheng
Publication year - 2002
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.800
Subject(s) - chemistry , chromatography , metabolite , liquid chromatography–mass spectrometry , mass spectrometry , tandem mass spectrometry , bioequivalence , fluoxetine , selected reaction monitoring , active metabolite , detection limit , pharmacokinetics , pharmacology , serotonin , medicine , biochemistry , receptor
Fluoxetine (F) and its N ‐demehylated metabolite norfluoxetine (NF) are selective inhibitors of serotonin reuptake in humans. A new sensitive rapid method for the simultaneous determination of F and NF in plasma was established and validated, and was further applied to assess the bioequivalence of two oral formulations of F in 22 healthy Chinese male volunteers who received a single oral dose of each formulation (containing 20 mg of fluoxetine hydrochloride). The new method involves using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode with deuterated fluoxetine (DF) as internal standard. High levels of analytical sensitivity and specificity of MS/MS detection enabled use of a simple liquid‐liquid extraction procedure. The combination of a simple sample clean‐up procedure and short chromatographic run‐time (5 min) considerably increased the productivity of the analytical method. The method was validated for the plasma concentration range 0.27–22 ng/mL for both of the test compounds, and the calibration curves were linear with coefficients of correlation >0.999. The limit of detection was 0.1 ng/mL for plasma F and NF. Taking the plasma sample size (200 µL) into account the new method for determination of F and NF is more sensitive than those described previously. Copyright © 2002 John Wiley & Sons, Ltd.