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

Abstract

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 ≤12%. Using a plasma sample size of 100 µl, the limits of detection were 7.0 nmol l-1 (2.0 ng ml-1) for hydromorphone, dihydromorphine and dihydroisomorphine and 11 nmol l-1 (5.0 ngml-1) for hydromorphone-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.