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Importance of Nor-naloxone Detection in Compliance Drug Monitoring of Suboxone Medication Assisted Treatment for Opioid Use Disorder

Pallavi Upadhyay, John Granger

Background: Suboxone (buprenorphine-naloxone combination drug) is prescribed for opioid use disorders (OUD) treatment. Naloxone (in suboxone) acts an antagonist to dissuade drug overdose. Medication compliance is key to OUD treatment. While there are several methodologies to assess compliance for buprenorphine, little has been studied regarding naloxone compliance monitoring issues. Our study sheds more light into the role of naloxone and nornaloxone in suboxone compliance monitoring and emphasizes the value of combined analysis of urine buprenorphine, norbuprenorphine, naloxone, and nor-naloxone, in medication compliance of OUD patients in suboxone medicationassisted treatment (MAT).

Method: UPLC-MS-MS was utilized to concurrently assess urinary buprenorphine, nor-buprenorphine, naloxone and nor-naloxone levels (limit of quantitation 0.1 ng/mL). Urine concentrations of these analytes were assessed in 3123 patients being treated for OUD employing suboxone MAT.

Results: Compliant patient intake of suboxone resulted in production of characteristic parent drug and metabolite patterns. In suboxone-prescribed patients, presence of buprenorphine and nor-buprenorphine (in an appropriate concentration ratio), and absence of naloxone and/or nor-naloxone, was indicative of non-compliance. Presence of buprenorphine and naloxone, in the absence of nor-buprenorphine and nor-naloxone, was also consistent with noncompliance.

Conclusions: Study demonstrated that naloxone sublingual absorption leads to nor-naloxone detection (above clinical cut-off levels). Presence of nor-naloxone in test results depicts a confirmation of naloxone absorption/ metabolism and renal excretion, hence can be used as an additional marker in suboxone compliance monitoring programs where drug adherence is an issue. We postulate that combined analysis of urinary buprenorphine, nor-buprenorphine, naloxone, and nor-naloxone, has clinical utility towards medication compliance assessments.