Improved detection of opioid use in chronic pain patients through monitoring of opioid glucuronides in urine.

When chronic pain patients are suspected of being non-compliant, their therapy can be withdrawn.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.

Ultra-low dose ketamine and memantine treatment for pain in an opioid-tolerant oncology patient.

Patients taking high-dose opioids chronically for tumor-related or neuropathic pain may develop pain that is refractory to opioids. One option for control of such pain is the use of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. We describe a case of opioid-refractory pain that responded to a low-dose IV infusion of ketamine in the inpatient setting. The patient was then successfully transitioned to oral memantine for long-term outpatient management, in a novel use of this oral NMDA receptor antagonist. We present recent findings from basic research on pain mechanisms to explain why opioid tolerance, as in this patient, may contribute to the analgesic benefit of NMDA receptor antagonists.