Development of a sensitive method for the determination of oxycodone and its major metabolites noroxycodone and oxymorphone in human plasma by liquid chromatography-tandem mass spectrometry

作者:Gaudette Fleur; Sirhan Daneau Andrea; St Onge Maude; Turgeon Jacques; Michaud Veronique*
来源:Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2016, 1008: 174-180.
DOI:10.1016/j.jchromb.2015.11.035

摘要

Oxycodone is an opioid agonist largely prescribed for the treatment of moderate to severe pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma levels of parent drug and its active metabolite, oxymorphone. For this purpose it is necessary to develop and validate a sensitive and selective analytical method for the quantification of oxycodone and its major metabolites, noroxycodone and oxymorphone, in human plasma. The analytical method consisted of a liquid-liquid extraction procedure followed by a high performance liquid chromatography with heated assisted electrospray ionization mass spectrometry (HPLC-HESI-MS/MS). The chromatographic separation was achieved using gradient elution with a mobile phase consisting of ethanol and 10 mM ammonium acetate on a Synergi MAX-RP analytical column (150 x 2 mm, 4 pm) protected by a security guard cartridge (C12 4 x 2 mm) at a flow rate of 300 mu L/min.The calibration functions are linear in the range of 300-50,000 pg/mL for oxycodone and noroxycodone and 50 to 10 000 pg/mL for oxymorphone. Intra- and inter-day relative standard deviations are less than 5.5% and 6.4%, respectively for all analytes. The limit of detection was 30 pg/mL for all analytes. We introduce a new HPLC-HESI-MS/MS sensitive and specific analytical method capable to simultaneously quantify oxycodone, noroxycodone and oxymorphone, in human plasma, and suitable for the conduct of pharmacokinetic studies after a single dose administration of the parent compound.

  • 出版日期2016-1-1