LC-MS-MS analysis of hydromorphone and hydromorphone metabolites with application to a pharmacokinetic study in the male Sprague-Dawley rat.

摘要

1. A high performance liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) assay was developed for the analysis of hydromorphone and its metabolites, namely dihydromorphine, dihydroisomorphine, hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide, in rat plasma samples. 2. Analytes were extracted by solid-phase extraction using C2 cartridges. The extraction recoveries were > 76% for all analytes. Both intra- and interassay variabilities were < or = 12%. Using a plasma sample size of 100 microl, the limits of detection were 7.0 nmol(-1) (2.0 ng ml(-1)) for hydromorphone, dihydromorphine and dihydroisomorphine and 11 nmol l(-1) (5.0 ng ml l(-1)) for hydrormorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorhine-3-glucuronide at a signal-to-noise ratio = 3. 3. The present assay was applied to a pharmacokinetic study in rat after intraperitoneal administration of hydromorphone.