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HPLC-MS/MS Based Time Course Analysis of Morphine and Morphine-6-Glucoronide in ICU Patients

Andreas E, Peter J, Lerch M, Schüttler J and Jeleazcov C

Morphine is a widely-used opioid analgesic to treat post-operative pain in the intensive care unit. For the quantification of morphine and its metabolite Glucuronide (M6G) concentrations a sensitive and specific liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated according to Food and Drug Administration (FDA) guidelines. Plasma samples were extracted with solid-phase extraction and substituted with deuterated morphine and M6G as internal standards. Separation was performed by gradient elution using UPLC-like system and analyzed by MS/MS consisting of an electrospray ionization source. The lower limit of quantification was 500 ‘‘pg/ml’’ for morphine and 50 ‘‘pg/ml’’ for M6G. Intra- and interassay precision and accuracy did not exceed ± 15%. The method was applied to a clinical study during intensive care treatment of patients after coronary artery bypass grafting and can serve for further pharmacokinetic studies.