Outcomes of Urine Drug Testing Results

There are four possible outcomes following a UDT: true positive, false positive, true negative, and false negative. True positive outcomes occur if the result of the test is positive and the substance is present in the urine. A false positive outcome occurs when the test is positive, but the substance is not present in the urine. True negative outcomes occur if the test is negative and the substance is not present in the urine, or if the concentration of the substance is below the cutoff concentration; alternatively, a false negative outcome occurs if the result is negative and the concentration of the substance is above the cutoff concentration. Table 1 summarizes possible outcomes of a UDT.

Table 1: Possible outcomes of a UDT


Positive Test

Negative Test

Drug Present

True Positive

False Negative

Drug Absent

False Positive

True Negative

Adapted from Reisfield et al. Ann Clin Lab Sci 2007.



The ability of a drug-class-specific immunoassay to detect a particular drug is dependent upon the similarity of the drug or its metabolite(s) to the standardization compound as well as the drug/metabolite's concentration in the urine compared to the standardization compound. While some immunoassays (e.g., cocaine) exhibit low cross-reactivity, other immunoassays, including amphetamines/methamphetamines tests, are highly cross-reactive. Table 2 identifies examples of cross-reacting compounds for certain immunoassays.

Table 2: Drug Cross-Reactants




NSAIDs, Proton pump inhibitors, Efavirenz


Poppy seeds, chlorpromazine, rifampin, dextromethorphan, quinine, verapamil and metabolites, quinolones


Ephedrine, methylphenidate, trazodone, bupropion, desipramine, amantadine, ranitidine, Vicks Vapor Spray


Chlorpromazine, thioridazine, meperidine, dextromethorphan, diphenhydramine, doxylamine, venlafaxine


Oxaprozin, some herbal agents, NSAIDs

List is not all-inclusive

Adapted from: Christo et al. Pain Physician 2011; Gourlay et al.

Available at http://www.familydocs.org/files/UDTMonograph_for_web.pdf

 Accessed 25 July 2012; Herring C et al. J Pharm Pract 2011.


Misleading True-Positive Results

Examples of true-positive results with a medical explanation are described below.

  • Opiates – Table 3 describes expected/potential metabolites of various opiates that may be present in the urine following use.

Table 3: Examples of Metabolism of Opiates


Expected/Potential Metabolites

Unexpected Metabolites (Metabolites that should

not be seen)



Morphine, Hydrocodone


  • Codeine, morphine, and hydrocodone may be present in the urine following codeine use
  • A prescription for morphine does not explain the presence of codeine (morphine is not metabolized to codeine)
  • Codeine is enzymatically converted to morphine via CYP2D6; UDT results in patients who lack CYP2D6 activity may only show codeine.



Codeine, hydrocodone

Morphine may be metabolized to produce small amounts (less than 10%) of hydromorphone



Morphine, Codeine

Hydrocodone may be metabolized to produce small amounts of hydromorphone



Hydrocodone, Codeine, Morphine

Oxycodone is enzymatically converted to oxymorphone via CYP2D6; if the urine of a patient prescribed oxycodone tests positive for oxymorphone, a quantitative analysis should confirm that the relative concentration of oxycodone is greater than oxymorphone



Anything other than hydromorphone

No known metabolites are detected by immunoassay at this time.

Adapted from: Christo et al. Pain Physician 2011; Gourlay et al.

Available at http://www.familydocs.org/files/UDTMonograph_for_web.pdf

Accessed 25 July 2012.



  • Cocaine is used as a topical anesthetic; a patient's urine may test positive for benzoylecgonine, cocaine's metabolite for up to 2-3 days following a procedure. In the absence of a medical explanation, a positive UDT for cocaine's metabolite should be interpreted as deliberate use.
  • There is no structural similarity between other topical anesthetics with the suffix "caine" (e.g., lidocaine, novicaine) and cocaine or its metabolite; as such, a cross-reaction does not occur.


  • The majority of amphetamine assays are designed to detect amphetamine, racemic compounds (e.g., dextroamphetamine, methamphetamine), and illicit analogues (e.g., methylenedioxymethaylamphetamine [MDMA], methylenedioxyethylamphetamine, and methylenedioxyamphetamine). Amphetamine assays have also been shown to detect structurally similar compounds, including stimulants, and have been shown to produce false-positive results. Consequently, clinical interpretation of positive amphetamine/methamphetamine results can be challenging because of the structural similarities to many prescription and OTC products.
  • Traditional GS/MS criteria for reporting a positive methamphetamine results is not sufficient to distinguish methamphetamine use from use of OTC products. In the case of disputed amphetamine or methamphetamine misuse, stereospecific chromatography may be used in addition to traditional GS/MS


Factors contributing to false-positive reports include technician/clerical error or cross-reactivity with other compounds found in the urine. Laboratory-based testing (e.g., GS/MS) is not influenced by cross-reacting compounds.


Factors contributing to false-negative reports include technician/clerical error or interference with the urine sample. Altering, substituting, or diluting a urine sample is a common technique to avoid detection of drug use. Urine characterization is based on appearance, temperature, pH, urinary creatinine concentration, and specific gravity. Additional factors that may affect UDT outcomes include drug detection times and drug pharmacodynamics. Understanding these factors can help clinicians to identify false negative results.

Urine Characteristics

  • Urine color is associated with the concentration of its components; concentrated samples are more reliable than dilute samples. In general, urine color ranges from pale yellow to clear; medications, foods, or diseases can result in unusually colored urine and should be recorded on documentation that accompanies the specimen. Specimens should be shaken to determine whether substances have been added (e.g., soap).
  • The temperature of a urine sample within 4 minutes of voiding should be between 32°C to 38°C (90°F to 100°F).
  • The normal urine pH range is 4.5 to 8.0. A pH level less than 3 or greater than 11 may be indicative of contamination; however, sample degradation due to improper storage or prolonged transport may result in a pH greater than 9.
  • Urine specimens consistent with human urine have a creatinine concentration greater than      20 mg/dL; concentrations less than 20 mg/dL are considered dilute and concentrations less than 5 mg/dL are not consistent with human urine.
  • A urine specific gravity less than 1.002 or greater than 1.02 is suggestive of an adulterated, diluted, or  a substituted specimen.

Drug Detection Times

Table 2 reports the length of time drugs of abuse can be detected in the urine. The detection time of a drug in urine is governed by several factors including dose, route of administration, presence of metabolites, urine volume and pH, patient variability (e.g., body mass), drug pharmacokinetics, and duration of use (i.e., short-term versus long-term use). In general, the detection time of most drugs in the urine is 1 to 3 days; however, lipophilic drugs (e.g., marijuana, diazepam, phencyclidine) may remain in the urine for a week or more, especially with long-term use.

Table 2: Approximate Length of Time of Detection of Substances in the Urine


Detection time in urine


7 to 12 hours


Up to 3 days


Short-acting (e.g., pentobarbital)

24 hours

Long-acting (e.g., phenobarbital)

3 weeks


Short-acting (e.g., lorazepam)

3 days

Long-acting (e.g., diazepam)

30 days

Cocaine metabolites (Benzoylecgonine)

2 to 4 days


Single Use

1 to 3 days

Chronic Use

Up to 30 days



48 hours

Heroin (morphine)

48 hours


2 to 4 days


3 days

EDDP (methadone metabolite)

Up to 6 days


48 to 72 hours


2 to 4 days


8 days

THC detection is dependent upon the grade and frequency of marijuana use

THC: delta-9-tetrahydrocannabinol; EDDP: 2-ethylidelen-1,5-dimethyl-3,3-diphenylpyrrolidine

Adapted from Moeller et al. Mayo Clin Proc 2008.


Drug Pharmacodynamics

Absorption, distribution, metabolism and elimination vary from patient to patient and may vary day-to-day within a given patient. Several studies have shown interindividual variability  in absorption and metabolism among several opioids, including morphine, hydromorphone, and meperidine. Additionally, numerous enzymes are involved in phase I and phase II metabolism. Individual patients may exhibit genetic polymorphisms in these enzymes; consequently, patients may be poor metabolizers, intermediate metabolizers, extensive or "normal" state metabolizers, or ultra-rapid metabolizers, all of which may affect a UDT result.