High-performance liquid chromatography mass spectrometry mass spectrometry analysis of morphine and morphine metabolites and its application to a pharmacokinetic study in male Sprague-Dawley rats

A high-performance liquid chromatography tandem mass spectrometry-mass spectrometry (LC-MS-MS) assay was developed for the analyses of morphine, morphine glucuronides and normorphine in plasma samples from rats. The analytes were extracted by using C-2 solid-phase extraction cartridges. The extraction recoveries were 100% for morphine, 84% for morphine-3-glucuronide, 64% for morphine-6-glucuronide and 88% for normorphine. Both intra- and inter-assay variabilities were below 11%. Using a plasma sample size of 100 mu l, the limits of detection were 13 nmol l(-1) (3.8 ng ml(-1)) for morphine, 12 nmol l(-1) (5.5 ng ml(-1)) for morphine-3-glucuronide, 26 nmol l(-1) (12 ng ml(-1)) for morphine-6-glucuronide and 18 nmol l(-1) (5.0 ng ml(-1)) for normorphine, at a signal-to-noise ratio of 3. The present assay was applied to a pharmacokinetic study in rats after intraperitoneal administration of morphine. (C) 1998 Elsevier Science B.V. All rights reserved.