title: Improved detection of opioid use in chronic pain patients through monitoring of opioid glucuronides in urine.
abstract: When chronic pain patients are suspected of being non-compliant, their therapy can be withdrawn. Therefore, sensitive and specific confirmatory testing is important for identifying diversion and adherence. This work aimed to develop a novel liquid chromatography tandem mass spectrometry (LC-MS-MS) method to detect 14 opioids and six opioid glucuronide metabolites in urine with minimal sample preparation. Analytes included were morphine, oxymorphone, hydromorphone, oxycodone, hydrocodone, codeine, fentanyl, norfentanyl, 6-monoacetylmorphine, meperidine, normeperidine, propoxyphene, methadone, buprenorphine, morphine-3-glucuronide, morphine-6-glucuronide, oxymorphone glucuronide, hydromorphone glucuronide, codeine-6-glucuronide and norbuprenorphine glucuronide. Samples were processed by centrifugation and diluted in equal volume with a deuterated internal standard containing 14 opioids and four opioid glucuronides. The separation of all compounds was complete in nine minutes. The assay was linear between 10 and 1,000 ng/mL (fentanyl 0.25-25 ng/mL). Intra-assay imprecision (500 ng/mL, fentanyl 12.5 ng/mL) ranged from 1.0 to 8.4% coefficient of variation. Inter-assay precision ranged from 2.9 to 6.0%. Recovery was determined by spiking five patient specimens with opioid and opioid glucuronide standards at 100 ng/mL (fentanyl 2.5 ng/mL). Recoveries ranged from 82 to 107% (median 98.9%). The method correlated with our current quantitative LC-MS-MS assay for opioids, which employs different chromatography. Internal standards were not available for every analyte to critically evaluate for ion suppression. Instead, a novel approach was designed to achieve the most rigorous quality control possible, in which the recovery of each analyte was evaluated in each negative sample.
authors: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors: Jane A
authors: JA
authors: Dickerson
authors: Thomas J
authors: TJ
authors: Laha
authors: Monica B
authors: MB
authors: Pagano
authors: Brendan R
authors: BR
authors: O'Donnell
authors: Andrew N
authors: AN
authors: Hoofnagle
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D059350:Chronic Pain / Q000188:drug therapy* / Q000652:urine; D016903:Drug Monitoring / Q000379:methods*; D020719:Glucuronides / Q000652:urine*; D006801:Humans; D009022:Morphine Derivatives / Q000652:urine; D010349:Patient Compliance; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D020719:Glucuronides; D009022:Morphine Derivatives