Urine is superior to oral fluid for detecting buprenorphine compliance in patients undergoing treatment for opioid addiction

Drug Alcohol Depend. 2019 Oct 1;203:8-12. doi: 10.1016/j.drugalcdep.2019.06.015. Epub 2019 Aug 1.


Background: Buprenorphine (BUP) is commonly used in opioid agonist medication-assisted treatment (OA-MAT). Oral fluid (OF) is an attractive option for compliance monitoring during OA-MAT as collections are observed and evidence suggests that OF is less likely to be adulterated than urine (UR). However, the clinical and analytical performance of each matrix for monitoring BUP compliance has not been well studied.

Methods: We collected 260 paired OF and UR specimens. Concentrations of buprenorphine (BUP) and norbuprenorphine (NBUP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in each matrix. The glucuronide metabolites and naloxone concentrations were also measured in UR by LC-MS/MS. Medications were reviewed and UR creatinine concentrations were determined.

Results: 147/260 specimens (57%) were positive for BUP and/or metabolites in one or both matrices. BUP and/or metabolites were more likely to be detected in UR (p < 0.001). 1 OF specimen and 12 UR specimens were considered adulterated/substituted. The majority of patients prescribed BUP were positive for BUP in UR (97%) as opposed to OF (78%). The detection of undisclosed use approximately doubled in UR.

Conclusions: UR is the preferred matrix for detecting both buprenorphine compliance and undisclosed use. Clinicians should consider the ease of collection, risk of adulteration and detection of illicit drug use when deciding on an appropriate matrix. If OF testing is clinically necessary, UR should be measured in conjunction with OF at least periodically to avoid false negative BUP results.

Keywords: Adulteration; Buprenorphine; Drug testing; LC–MS/MS; Medication compliance; Opioid addiction; Oral fluid; Urine.

MeSH terms

  • Buprenorphine / analogs & derivatives*
  • Buprenorphine / metabolism*
  • Buprenorphine / urine*
  • Chromatography, Liquid
  • Creatinine / urine
  • Humans
  • Naloxone / urine
  • Narcotic Antagonists / metabolism
  • Narcotic Antagonists / urine
  • Patient Compliance / statistics & numerical data*
  • Saliva / metabolism*
  • Tandem Mass Spectrometry


  • Narcotic Antagonists
  • Naloxone
  • Buprenorphine
  • norbuprenorphine
  • Creatinine