title: Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: application to a clinical pharmacokinetic study.
abstract: 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.
authors.affiliation: College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Qiongfeng
authors.initials: Q
authors.lastname: Liao
authors.forename: Yating
authors.initials: Y
authors.lastname: Deng
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.forename: Biyan
authors.initials: B
authors.lastname: Pan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D003061:Codeine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D015394:Molecular Structure; D009020:Morphine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors
chemical_list: D009020:Morphine; D003061:Codeine