Whether oral fluid should replace urine as the gold standard to assess medication compliance is an ongoing debate. This topic was discussed, among other places, in a recent article and at the 2018 AACC annual meeting.1 At the annual meeting, Dr. Athena Petrides and I took opposite stances, one illustrating the superiority of oral fluid and the other claiming that urine should remain the leader. Although the audience did not officially vote on the 'winner', the questions and comments suggested a tie.

Can drug properties predict which drugs will be detected well in oral fluid and guide selection of a matrix? Oral fluid has a pH of approximately 6.0-6.5 therefore weak bases such as 6-acetylmorphine (6-AM; the unique heroin metabolite) should ionize and become trapped. However, heavily glucuronidated drugs such as oxymorphone should not cross into oral fluid. Our study has shown that drug properties are helpful to guide decision-making.2

Oral fluid is superior. Have you looked at your urine creatinine concentrations and seen a bimodal peak suggesting dilute/adulterated urines? If yes, you may want to use oral fluid. Oral fluid allows observed collections. It is also more convenient for the patients especially if they cannot provide urine or need to travel to another location to provide the specimen. Furthermore, oral fluid is more reflective of blood/therapeutic concentrations. For those of you concerned about cost, oral fluid allows you to eliminate adulteration testing saving both time and money. When we polled the audience at the annual meeting, 48% of sites measure urine temperature at the time of collection, 61% perform creatinine and/or specific gravity and 23% perform nitrites and/or oxidant testing. Finally, oral fluid detects drugs of abuse well. The detection rate of 6-AM2 and amphetamine (unpublished data) is higher in oral fluid. Are those drugs important for you to detect?

No, urine is superior. We have more experience with urine and scientific guidelines state that urine is the gold standard until proven otherwise.3 The windows of the detection in urine are more well-defined and clinicians are less likely to miss remote drug use. Furthermore, oral fluid collection devices are fraught with headaches. Training clinicians and validating the device can be laborious. There may be issues with inadequate sample volumes especially in patients with xerostomia (a side effect of some medications). Despite the opinion of 17% of our audience at the annual meeting, buccal contamination or other interferents/adulterants are possible with oral fluid. Importantly, both parent drugs and metabolites can be detected in urine allowing better assessment of compliance. In our study, many drugs were preferentially detected in urine; 7-aminoclonazepam, lorazepam, oxazepam, oxymorphone, hydromorphone.2 Our unpublished data also suggest that detection of buprenorphine and cocaine is superior in urine. Take that oral fluid!

Other interesting points were raised at the annual meeting and in our Clinical Chemistry article.1 One was the utility of blood as opposed to either urine or oral fluid. Although it is more invasive to collect, blood avoids buccal contamination and windows of detection are similar to oral fluid. The preferred matrix for workplace drug testing, in which the employee should be negative for drugs, was also discussed. The availability of negative synthetic urine and ease with which employees can 'beat the system' when the collections are not observed has pushed this testing area towards oral fluid.

Reflective of our lack of consensus in the urine vs. oral fluid debate and as stated in a recent white paper “the most important challenge in drug testing is not to identify every drug that we are technologically capable of detecting, but to do medically necessary and accurate testing for those drugs that are most likely to impact clinical decisions”.4 We suspect the patient population and clinical needs will drive the decision between oral fluid, urine or even other matrices and the limitations of the chosen matrix will need to be communicated and addressed. Is it time for you to make a change to your drug testing algorithm to assess compliance?


  1. Melanson SEF, Clarke WA, Fragoza K, Gilligan C, Holdren R, Jannetto PJ, Magnani B, Moore C. Debates in pain management testing. Clinical Chemistry, 2018;64:769-776.
  2. Petrides AK, Melanson SEF, Kantartjis M, Le RD, Demetriou CA, Flood JG. Monitoring Opioid and Benzodiazepine Use and Abuse: Is Oral Fluid or Urine the Preferred Specimen Type? Clin Chim Acta, 2018;481:75-82.
  3. Jannetto PJ, Bratanow N, Clark WA, Hamill-Ruth RJ, Hammett-Stabler CA, Huestis MA, Kassed CA, McMillin GA, Melanson SE, Langman LJ. Executive Summary AACC LMPG: Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients. J Applied Lab Med, 2018;2:489-526.
  4. https://www.asam.org/docs/default-source/public-policy-statements/drug-testing-a-white-paper-by-asam.pdf