Our in-house pain management urine drug test is composed of a qualitative LC-MS/MS only opioid profile with low cutoffs for positivity combined with a standard screen and confirm approach for drugs of abuse. In rare cases, individuals with relatively large quantities of oxycodone in their urine have a small quantity of morphine that is concurrently detected. Discussion with pain management providers suggest that these individuals have a history compliance with prescribed medications and abstinence from non-prescribed substances. Review of method settings and results for contrived specimens does not suggest an analytical problem. Send out testing of these specimens to a referral lab that performs LC-MS/MS opioid testing using the same cutoffs for positivity typically returns an “interfering substance” comment for morphine results. This problem is complicated by the fact that some individuals at our institution are co-prescribed morphine and oxycodone, whereas others are only prescribed oxycodone only. Review of literature suggests that minor (unmonitored) metabolites of oxycodone may undergo in-source fragmentation to produce morphine isobars.
Rare cases of co-positivity for morphine and oxycodone in individuals taking oxycodone only.
•Dilute and shoot, 5μL injection
•Waters Acquity UPLC, 2.1x150 mm, 1.8μM C18 column
•Waters Xevo TQD, MRM acquisition, qualitative reporting
•8 minute linear gradient (0.4mL/min flow rate, 50°C column temp)
•Opioid Cutoffs for positivity:
•25 ng/mL: Morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, tramadol, O-desmethyltramadol, tapentadol, Methadone, EDDP
•10 ng/mL: 6-acetylmorphine and naloxone
•5 ng/mL: Buprenorphine and Norbuprenorphine
•All other drug classes tested by standard screen and confirm approach
•Review of method settings and analysis of contrived specimens did not correct the problem. Nor did further separation of morphine and oxycodone acquisitions in time. Investigation suggests morphine is most likely real. While it may be present for several reasons, co-positivity with oxycodone may indicate in-source fragmentation of a minor metabolite of oxycodone that results in production of a morphine isobar .
•Currently, any pain management specimen that is co-positive for oxycodone and morphine requires a positive opiate immunoassay result in order to report morphine.
 A.C. Muñoz-Muñoz, T. Pekol, D. Schubring, C. Johnson, L. Andrade, Identification of Novel Opioid Interferences using High-Resolution Mass Spectrometry, J Anal Toxicol 42(1) (2018) 6-16.