title: 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.
abstract: 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 10mM ammonium acetate on a Synergi MAX-RP analytical column (150×2mm, 4μm) protected by a security guard cartridge (C12 4×2mm) at a flow rate of 300μL/min.The calibration functions are linear in the range of 300-50,000pg/mL for oxycodone and noroxycodone and 50 to 10 000pg/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 30pg/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.
authors.affiliation: CRCHUM, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Fleur
authors.initials: F
authors.lastname: Gaudette
authors.affiliation: CRCHUM, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Andréa
authors.initials: A
authors.lastname: Sirhan-Daneau
authors.affiliation: CRCHUM, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Maude
authors.initials: M
authors.lastname: St-Onge
authors.affiliation: CRCHUM, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
authors.affiliation: CRCHUM, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada. Electronic address: v.michaud@umontreal.ca.
authors.forename: Veronique
authors.initials: V
authors.lastname: Michaud
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D009019:Morphinans / Q000097:blood*; D010098:Oxycodone / Q000097:blood*; D010111:Oxymorphone / Q000097:blood*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D009019:Morphinans; C077256:noroxycodone; D010111:Oxymorphone; D010098:Oxycodone
keywords: Human; Liquid chromatography; Mass spectrometry; Noroxycodone; Oxycodone; Oxymorphone; Plasma