Evaluation of adherence monitoring in buprenorphine treatment: A pilot study using timed drug assays to determine accuracy of testing

Br J Clin Pharmacol. 2023 Jul;89(7):1938-1947. doi: 10.1111/bcp.15318. Epub 2022 Mar 31.


Aims: Buprenorphine is effective at reducing relapse to opioid misuse, morbidity and mortality in opioid-dependent patients. Urine drug screening (UDS) to assess adherence is used routinely in opioid agonist treatment (OAT). The primary aim of this study was to determine factors which may be associated with a negative qualitative urine drug screen for buprenorphine in OAT patients.

Methods: This prospective pilot study was conducted at a tertiary addiction medicine centre. Twenty participants on stable treatment underwent supervised administration of sublingual buprenorphine. Matched urine and blood samples were collected prior to and 2, 4 and 6 hours after buprenorphine administration. Qualitative urine drug screen results were obtained using gas chromatography-mass spectrometry (GC-MS), while quantitative blood and urine results were obtained using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results: Qualitative urine assay yielded a negative result for buprenorphine in 57% of tested samples. The median concentration of urinary buprenorphine was 167 mcg/L (range: 2-1730 mcg/L). Thirty percent of all blood samples did not detect buprenorphine (range 0-18 mcg/L). Positive qualitative urine drug screen results were associated with higher urine (343 mcg/L compared with 75 mcg/L; P < .05) and blood (4 mcg/L compared with 2 mcg/L; P < .05) buprenorphine concentrations. Median urine concentrations of buprenorphine were highest at 2 hours and were higher in participants receiving CYP3A4 inhibitors.

Conclusion: Interpretation of qualitative urine drug screens to assess adherence in OAT is complex. Poor adherence with treatment cannot be assumed in patients returning a negative qualitative GC-MS urine drug screen.

Keywords: addiction; mass spectrometry; opioids.

MeSH terms

  • Analgesics, Opioid
  • Buprenorphine* / therapeutic use
  • Chromatography, Liquid / methods
  • Humans
  • Medication Adherence
  • Pilot Projects
  • Prospective Studies
  • Tandem Mass Spectrometry


  • Buprenorphine
  • Analgesics, Opioid

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