The Role of Opioid Metabolic Pathways in Interpreting Urine Drug Testing Results

Significant psychosocial and treatment repercussions to patients may occur when clinicians misinterpret the results of drug testing, including loss of employment or housing, revocation of parole or probation status, removal of children from the home, and dismissal from a medical practice.[1] Clinicians who order and use urine drug screen (UDS) immunoassays in their clinical practice are often aware that they must confirm a positive UDS result by ordering a highly sensitive and specific liquid chromatography-mass spectrometry (LC-MS) confirmatory test.[2,3] However, there is limited literature regarding the misinterpretation of LC-MS confirmatory drug testing results by physicians,[4,5] and it is not known how frequently such misinterpretation of confirmatory testing occurs in addiction clinical practice. Since confirmatory tests commonly measure the urine concentrations of both parent drugs and their metabolites, an understanding of the pharmacokinetics of these drugs is essential for proper interpretation of such testing.[4] Unfortunately, the limited literature available suggests that clinicians who encounter difficulty with interpreting urine drug testing results of both types may be unaware that they can seek help from expert consultants such as clinical chemists or medical toxicologists.[4,5]The aim of this focus session is to provide attendees with the knowledge needed to interpret both UDS and confirmatory urine drug testing of opioids. The session will begin with an overview of opiates, semi-synthetic opioids, and synthetic opioids, which will provide the background for listeners to understand which opioids can reliably be detected by a standard opiate UDS and which cannot. This will be followed by a brief discussion of the principles of LC-MS confirmatory testing to allow attendees to understand why these tests are so much more sensitive and specific than UDS immunoassays, as well as the benefits and pitfalls of using such sensitive technology to monitor patient substance use. The final portion of the session will demonstrate to attendees how opioid manufacturing contaminants and metabolites may be detected on the highly sensitive LC-MS and possibly lead an unsuspecting practitioner to an erroneous conclusion regarding patient substance use. This will include literature-reported examples of detectable opioid manufacturing contaminants, as well as a discussion of the metabolites of commonly tested-for opioids such as methadone, buprenorphine, and fentanyl. Case examples will be provided throughout the session to reinforce points and engage the audience. Although a table of commonly encountered opioids and their expected metabolites and contaminants will be provided as a reference tool, the session will focus on higher-level understanding and improvement of urine drug testing interpretation skills using knowledge of opioid pharmacology and metabolites. Participants will also be advised regarding accessing resources and reaching expert consultants when needed.