Monitoring opioid and benzodiazepine use and abuse: Is oral fluid or urine the preferred specimen type?

Clin Chim Acta. 2018 Jun;481:75-82. doi: 10.1016/j.cca.2018.02.034. Epub 2018 Feb 27.


Background: Oral fluid (OF) has become an increasingly popular matrix to assess compliance in pain management and addiction settings as it reduces the likelihood of adulteration. However, drug concentrations and windows of detection are not as well studied in OF as in urine (UR). We compared the clinical utility and analytical performance of OF and UR as matrices for detecting common benzodiazepines and opioids.

Methods: OF and UR concentrations of 5 benzodiazepines and 7 opioids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 263 paired OF and UR specimens. UR creatinine was measured and prescription medications were reviewed.

Results: The benzodiazepines 7-aminoclonazepam, lorazepam, and oxazepam exhibited statistically higher detection rates in UR. For opioids, 6-AM was statistically more likely to be detected in OF, while hydromorphone and oxymorphone were statistically more likely to be detected in UR. Chemical properties including glucuronidation explain preferential detection in each matrix, not UR creatinine nor prescription status.

Conclusion: We found that OF is the preferred matrix for 6-AM, while UR is preferred for 7-aminoclonazepam, lorazepam, oxazepam, hydromorphone, and oxymorphone. However, OF should be considered if the risk of adulteration is high and use and/or misuse of benzodiazepines, hydromorphone, and oxymorphone is low.

Keywords: Benzodiazepine; Liquid chromatography-tandem mass spectrometry; Opioid; Oral fluid drug testing; Pain management; Urine drug testing.

MeSH terms

  • Analgesics, Opioid / analysis*
  • Benzodiazepines / analysis*
  • Body Fluids / chemistry*
  • Chromatography, Liquid
  • Humans
  • Substance Abuse Detection*
  • Tandem Mass Spectrometry
  • Urinalysis*


  • Analgesics, Opioid
  • Benzodiazepines