Further inquiry will clarify these concerns. Clinicians should educate patients and manage accordingly. Confirmatory tests may be ordered upon clinicians’ discretion.
Urine sample tampering. Dilution or substitution of urine samples may lead to unexpected negative results. Usually, the urine sample will have abnormal parameters, including temperature, pH, specific gravity, urine creatinine level, or detection of adulterants. If needed, consider observed urine sample collection. Jaffee et al25 reviewed tampering methods in urine drug testing.
Diversion or binge use of medications. If patients adamantly deny diverting or binge using their medication, order confirmatory tests. If the confirmatory test also is negative, modify the treatment plan accordingly, and consider the following options:
- adjust the medication dosage or frequency
- discontinue the medication
- conduct pill counts for more definitive evidence of diversion or misuse, especially if discontinuation may lead to potential harm (for example, for patients prescribed buprenorphine for opioid use disorder).
When to order confirmatory tests for unexpected negative results.
Because confirmatory tests also measure drug concentrations, clinicians sometimes order serial confirmatory testing to monitor lipophilic drugs after a patient reports discontinuation, such as in the case of a patient using marijuana, ketamine, or alprazolam. The level of a lipophilic drug, such as these 3, should continue to decline if the patient has discontinued using it. However, because the drug level is affected by how concentrated the urine samples are, it is necessary to compare the ratios of drug levels over urine creatinine levels.26 Another use for confirmatory-quantitative testing is to detect “urine spiking,”27,28 when a patient adds an unconsumed drug to his/her urine sample to produce a positive result without actually taking the drug (Box 3).
Box 3
On a confirmatory urine drug test, a patient taking buprenorphine/naloxone had a very high level of buprenorphine, but almost no norbuprenorphine (a metabolite of buprenorphine). After further discussion with the clinician, the patient admitted that he had dipped his buprenorphine/naltrexone pill in his urine sample (“spiking”) to disguise the fact that he stopped taking buprenorphine/naloxone several days ago in an effort to get high from taking opioids.
When to consult lab specialists
Because many clinicians may find it challenging to stay abreast of all of the factors necessary to properly interpret UDT results, consulting with qualified laboratory professionals is appropriate when needed. For example, a patient was prescribed codeine, and his UDTs showed morphine as anticipated; however, the prescribing clinician suspected that the patient was also using heroin. In this case, consultation with a specialist may be warranted to look for 6-mono-acetylemorphine (6-MAM, a unique heroin metabolite) and/or the ratio of morphine to codeine.
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