A patient with opioid use disorder is receiving buprenorphine. Treatment adherence is monitored using urine drug testing. Detection of which of the following in this patient’s urine sample would MOST likely indicate that it had been adulterated?

  • □ (A) Buprenorphine
  • □ (B) Low levels of norbuprenorphine
  • □ (C) Low levels of thebaine
Buprenorphine is a semisynthetic opioid derived from thebaine. It is a partial agonist at the μ-opioid receptor and an antagonist at the μ-opioid receptor. Buprenorphine is used in the treatment of opioid use disorder in sublingual, buccal, and subcutaneous implant formulations. The medication is metabolized by N-dealkylation via the liver cytochrome P450 (CYP) 3A4 enzyme and glucuronidation. Buprenorphine’s metabolites include buprenorphine-3-glucuroide, norbuprenorphine, and norbuprenorphine-3-glucuronide. Most excretion is via the feces. Buprenorphine is expected to be detected in the urine; this would not suggest adulteration of the sample.

Norbuprenorphine is an active metabolite of buprenorphine and can be detected during urine testing via gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry assays. Of note, adulterated urine specimens, where buprenorphine has been added directly to the urine sample, have higher buprenorphine and lower norbuprenorphine levels compared to unadulterated urine specimens from patients taking buprenorphine.

Thebaine in the urine would suggest poppyseed consumption but would not indicate adulteration of the sample.

Answer: B