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Rapid simultaneous determination of codeine and morphine in plasma using LC‐ESI‐MS/MS: Application to a clinical pharmacokinetic study
Author(s) -
Liao Qiongfeng,
Deng Yating,
Xie Zhiyong,
Pan Biyan,
Zhang Lei
Publication year - 2009
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200800417
Subject(s) - codeine , chromatography , chemistry , pharmacokinetics , analyte , morphine , metabolite , selected reaction monitoring , electrospray ionization , mass spectrometry , electrospray , tandem mass spectrometry , pharmacology , medicine , biochemistry
A rapid and sensitive high‐performance LC‐MS/MS method was developed and validated for the simultaneous quantification of codeine and its metabolite morphine in human plasma using donepezil as an internal standard (IS). Following a single liquid‐liquid extraction with ethyl acetate, the analytes were separated using an isocratic mobile phase on a C 18 column and analyzed by MS/MS in the selected reaction monitoring mode using the respective [M+H] + ions, mass‐to‐charge ratio ( m/z ) 300/165 for codeine, m / z 286/165 for morphine and m / z 380/91 for IS. The method exhibited a linear dynamic range of 0.2–100/0.5–250 ng/mL for codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5 ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated LC‐MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate.