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

Autor: Qingxiang Shao, Zhouhua Ji, Meiyun Zhang, Cheng Yu, Jieyu Dai, Ping Liu, Fang Xu, Jiang Zhen, Hao Yuan, Bin Huang, Chuan Li, Fajun Nan, Jian Cui
Rok vydání: 2002
Předmět:
Zdroj: Rapid communications in mass spectrometry : RCM. 16(19)
ISSN: 0951-4198
Popis: 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.
Databáze: OpenAIRE