Oxymorphone

Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.[Pubmed:28080998]

Clin Chem Lab Med. 2017 Aug 28;55(9):1324-1331.

BACKGROUND: Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, Oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and Oxymorphone. METHODS: Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). RESULTS: Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study. CONCLUSIONS: Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.

Analysis of Intensive Care Unit Admission and Sequelae in Patients Intravenously Abusing Extended-Release Oral Oxymorphone.[Pubmed:28257549]

South Med J. 2017 Mar;110(3):217-222.

OBJECTIVES: Prescription drug abuse is a major public health problem in the United States, with the rate of opioid-related deaths nearly quadrupling between 2000 and 2014. Extended-release oral Oxymorphone hydrochloride (Opana ER) is a long-acting opioid prescribed for chronic pain; however, it also has the potential to be abused via intravenous injection. This retrospective review sought to analyze specific complications and sequelae requiring intensive care unit resources for patients intravenously abusing extended-release oral Oxymorphone. METHODS: We retrospectively reviewed the medical records of patients identified for drug abuse between January 2012 and December 2015, identifying patients who intravenously abused extended-release oral Oxymorphone. Medical charts were reviewed to identify associated sequelae and patients requiring an intensive care unit level of care. RESULTS: We identified 53 patients who required treatment in an intensive care unit setting as a consequence of intravenously abusing extended-release oral Oxymorphone. Twenty-eight patients (52.8%) required endotracheal intubation with mechanical ventilation for either acute hypoxic respiratory failure or protection of airway. Acute kidney injury developed in 48 patients (90.6%); 28.3% of these patients failed to regain renal function and required renal replacement therapy. Bacteremia was diagnosed in 36 patients (67.9%) and 30 patients (56.6%) were diagnosed as having acute infective bacterial endocarditis. CONCLUSIONS: Our patients demonstrated a great need for critical care resources and severe sequelae related to intravenous drug abuse. Clinicians should be vigilant for the possibility for clinical decompensation when initially evaluating patients reporting intravenous abuse of extended-release oral Oxymorphone.

Characterization of [(3)H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice.[Pubmed:28192197]

Neurosci Lett. 2017 Mar 16;643:16-21.

Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear. This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of Oxymorphone binding sites in the brain. Saturation binding studies using [(3)H]Oxymorphone revealed high affinity binding sites in mouse brain displaying Kd of 1.7nM and Bmax of 147fmol/mg. Furthermore, we performed quantitative autoradiography binding studies using [(3)H]Oxymorphone in mouse brain. The distribution of [(3)H]Oxymorphone binding sites was found to be similar to the selective MOP agonist [(3)H]DAMGO in the mouse brain. [(3)H]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [(3)H]Oxymorphone binding sites suggesting Oxymorphone may not target DOP or KOP. These results confirm that the MOP, and not the DOP or the KOP is the main high affinity binding target for Oxymorphone.