Rapid simultaneous determination of codeine and morphine in plasma using LC‐ESI‐MS/MS: Application to a clinical pharmacokinetic study |
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Authors: | Qiongfeng Liao Yating Deng Zhiyong Xie Biyan Pan Lei Zhang |
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Affiliation: | 1. College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China;2. Laboratory of Pharmaceutical Analysis and Quality Assessment, School of Pharmaceutical Sciences, Sun Yat‐sen University, Guangzhou, China. Fax: +86‐20‐8733‐4718;3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China |
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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 C18 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. |
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Keywords: | Codeine Determination LC‐MS/MS Morphine Pharmacokinetics |
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