2009
DOI: 10.1002/jssc.200800417
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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 28… Show more

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Cited by 24 publications
(12 citation statements)
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“…However, this approach compromises the cleanliness of the samples, and it is not economical due to damage to the column and potential contamination of the detector. Although liquid-liquid extraction produces cleaner plasma sample extracts, and it has been used successfully for quantification of midazolam and its two metabolites [21,24,25], as well as fentanyl and norfentanyl in plasma samples [19], it is an expensive and labour intensive method using very toxic solvents such as toluene for fentanyl, norfentanyl [19] and midazolam [25], ethyl acetate for morphine and its glucuronide metabolites [26], or hexane for midazolam [21,24].…”
Section: Methods Development For Lc and On-line Spementioning
confidence: 99%
“…However, this approach compromises the cleanliness of the samples, and it is not economical due to damage to the column and potential contamination of the detector. Although liquid-liquid extraction produces cleaner plasma sample extracts, and it has been used successfully for quantification of midazolam and its two metabolites [21,24,25], as well as fentanyl and norfentanyl in plasma samples [19], it is an expensive and labour intensive method using very toxic solvents such as toluene for fentanyl, norfentanyl [19] and midazolam [25], ethyl acetate for morphine and its glucuronide metabolites [26], or hexane for midazolam [21,24].…”
Section: Methods Development For Lc and On-line Spementioning
confidence: 99%
“…This method awards compensation over those previously reported [6][7][8][9][10][11][12][13]23 in terms of time per sample clean-up, improved separation speed by monolithic column and high-throughput due to fast chromatographic run time synchronized to sample extraction (3.0 min). On-line SPE-LC-MS/MS method allowed a rapid assay development and sample processing.…”
Section: Discussionmentioning
confidence: 92%
“…However, such methods were performed in other matrices and sample extraction steps were semi-automated. 6,18-22 Liao et al 23 developed a codeine determination method with chromatographic run time of 2 min and applied it successfully to a bioequivalence study. In spite of results achieved in relation to recovery of about 80%, the method based on liquid-liquid extraction consists of several steps to clean samples, including 15 min mixing, 10 min centrifugation, plus solvent evaporation time at 40 °C.…”
Section: On-line Spe Processmentioning
confidence: 99%
“…There are several methods used to detect morphine or its main metabolites M3G and M6G in animal tissues, but not in brain samples [19][20][21][22][23][24]. However, most of them used different molecules as internal standard (IS) such as donepezil, codeine, and naloxone hydrochloride [19][20][21][22].…”
Section: Introductionmentioning
confidence: 99%
“…However, most of them used different molecules as internal standard (IS) such as donepezil, codeine, and naloxone hydrochloride [19][20][21][22]. There are large differences in the physical and chemical properties among gemfibrozil, morphine, and morphine metabolites.…”
Section: Introductionmentioning
confidence: 99%