title: Simultaneous analysis of codeine and its active metabolites in human plasma using liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study after oral administration of codeine.
abstract: A rapid and sensitive bioassay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the simultaneous determination of codeine and its active metabolites, including morphine, morphine 3β-glucuronide (M3G) and morphine 6β-glucuronide (M6G), in human plasma. Sample preparation of plasma after the addition of naloxone as internal standard (IS) involved solid-phase extraction (SPE) on C18 cartridges. Reversed-phase chromatography using a gradient elution with methanol and 0.04% formic acid solution (pH 3.5) was used for separation in a run time of 5 min. The analytes were detected in the positive ion mode using multiple reaction monitoring (MRM) of the transitions at m/z 300.4→215.2 for codeine, 286.2→152.0 for morphine, and 462.2→286.2 for M3G and M6G. The method has the following performance characteristics: a reliable response range of 0.05-80 ng/ml for codeine, M3G and M6G and a response range of 0.05-5.0 ng/ml for morphine with correlation coefficients (r) of >0.997 for all analytes. The lower limit of quantitation (LLOQ) for all four analytes was 0.05 ng/ml. The intra- and inter-day precision and accuracy of the quality control samples at low, medium and high concentration levels showed <12% relative standard deviation (RSD) and -6.9 to 8.1% relative error (RE) for all the analytes. The method was successfully applied to a pharmacokinetic study of codeine in healthy Mongolian Chinese volunteers after a 30 mg oral dose.
authors.affiliation: Department of Pharmacy, Shenyang Northern Hospital, Shenyang 110016, PR China.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Wu
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Bai
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D003061:Codeine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D003061:Codeine