Buprenorphine is a partial mu-opioid agonist and kappa antagonist used to treat opioid use disorder, usually as a sublingual film or tablet combined with naloxone (Suboxone) to deter injection. Monitoring confirms adherence and can flag diversion; LC-MS/MS measures buprenorphine, its active metabolite norbuprenorphine, and naloxone.¹

In MAT monitoring, the pattern of analytes matters as much as the positive result: buprenorphine with its metabolite norbuprenorphine supports genuine dosing, whereas a very high buprenorphine level with almost no norbuprenorphine can indicate that drug was added directly to the specimen ('shaving').² The interpretation grid summarizes these patterns.

LC-MS/MS quantifies buprenorphine, norbuprenorphine (active metabolite), and naloxone in urine, and buprenorphine in oral fluid. The presence of norbuprenorphine supports genuine ingestion, whereas high parent drug with little metabolite suggests direct addition to the sample.² Low-dose formulations (Butrans, Belbuca) may fall below detection.¹ For oral fluid, patients should avoid dosing for about an hour before collection to prevent falsely high concentrations.³

• Interpret buprenorphine results using the norbuprenorphine-to-buprenorphine ratio, not the parent level alone.²
• Consider 'shaving' when buprenorphine is very high with minimal norbuprenorphine (see the grid).²
• Use observed or oral-fluid collection when specimen tampering is suspected.³
• Recognize that low-dose pain formulations may be undetectable; a negative does not always mean non-adherence.¹
• Account for CYP3A4 inhibitors or inducers that alter buprenorphine metabolism.