Frequently Asked Questions

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    Interpretation of results

  • Does a positive (negative) test result mean that the patient did (did not) take the prescribed drug?

    It depends. Many factors affect the test result including the patient, the specimen, as well as the laboratory test itself. Any result that is not consistent with expectation should be confirmed by another method, and investigated so you can be confident about the interpretation. The laboratory can be a partner to you in helping guide an appropriate investigation.
  • What does it mean when a parent drug is identified in the absence of any drug metabolites?

    Most drugs are metabolized in the body, and it is the metabolites that appear most commonly in the urine. As such, the presence of parent drug in the absence of metabolites is unusual and could indicate that the drug was added directly to the urine. Specific questions about adulteration of a specimen with parent drug should be discussed with the testing laboratory. It is also possible that patients are unable to metabolize drugs due to genetic variation, impaired liver function, or drug-drug interactions.
  • How should patterns of drug metabolites be interpreted?

    Many drugs are eliminated and detected based on common patterns. For example, diazepam usually appears in the urine as a combination of nordiazepam, oxazepam, and temazepam. For buprenorphine, the norbuprenorphine glucuronide metabolite is most prominently observed. If the expected metabolite pattern is observed, it provides confidence that the drug was taken. It may also help determine the specific drug taken, as well as the approximate timing of the last drug administration. Specific questions about patterns of metabolites for a specific drug should be discussed with the testing laboratory.
  • Can urine concentrations be used to determine what dose a patient took?

    Not precisely. While drug concentrations in urine generally correlate with the dosage of drug taken, the correlation is not precise because of variation in amount of drug eliminated in the urine over time, variation in the concentration of urine, and pharmacokinetic differences. Evaluation of timed blood concentrations, as per the fundamentals of therapeutic drug monitoring, is the preferred approach to estimating dose.
    For further reading on this topic (based on example of fentanyl), refer to (http://www.ncbi.nlm.nih.gov/pubmed/20297612) and (http://www.ncbi.nlm.nih.gov/pubmed/15516290)
  • I know my patient is taking buprenorphine (fentanyl, meperidine, tramadol) but the screen result for “opiates” came back negative. Why?

    The opiate immunoassay in screen panels detect a rather limited number of analytes, and normally do not cross-react with other opioids such as buprenorphine, fentanyl, meperidine, tapentadol, or tramadol. The opiate immunoassays typically detect only codeine, hydrocodone, hydromorphone, morphine and the heroin metabolite (6-AM). This is true for point-of-care screens (cups or dipsticks) and for laboratory immunoassays. In order to verify presence of drugs not represented or poorly detected in the immunoassay panel, order a mass spectrometry-based test with proven performance for the specific drug of interest, such as quantitative LC-MS/MS tests or the high-resolution hybrid screen using LC-TOF technology. See test menu
  • How can you tell if a patient has added drug directly to his/her urine to mimic compliance?

    In urine, detecting a large amount of parent drug without (or with very little) drug metabolites usually indicates that the patient has added drug directly to his/her urine specimen (spiked, adulterated). This type of specimen adulteration may not be detected with a drug screen, but can be detected by ARUP’s mass spectrometry tests that independently measure parent drug and common drug metabolite(s). Our buprenorphine paper shows examples of the use of metabolite data in the detection of specimen adulteration. The lack of drug metabolites, however, does not always indicate adulteration: in rare cases, parent drug has been found without metabolite in urine of patients with compromised metabolism. In these cases the concentration of parent drug is relatively low compared to an adulterated sample.

    Performance & Limitations of tests

  • How long can you detect a drug after use?

    The duration of time for which a drug can be detected is based on
    (1) the pharmacokinetics of the drug itself,
    (2) the dose and frequency of dosing,
    (3) detection limits of the test utilized, and
    (4) the quality of the specimen being tested.
    Most drugs are detected in urine for 24-48 hours after last use. Some drugs are detected for shorter durations (e.g. methylphenidate, some benzodiazepines) and others for much longer (e.g. methadone, marijuana). Contact the laboratory for estimates on detection periods for a specific drug, or consult the half life and detection chart.
  • What is the false positive rate of a drug screen?

    False positive rates in automated urine immunoassays are generally <5%, with the exception of amphetamines, which are notorious for false positives. Immunoassays used in point-of-care devices such as urine cups tend to have lot-to-lot variability and poor performance as well. As such, when using a cup, one must balance convenience and speed with the possibility of having to confirm results when they do not match clinical expectations more often. In urine drug screen cups, a positive result for methamphetamine should be considered a false positive unless its metabolite amphetamine is also positive. False positives are very rare In a mass spectrometry-based screen using time-of-flight (TOF) technology.
  • Will amphetamine tests detect racemic methylphenidate (Ritalin) or d-methylphenidate (Focalin, dexmethylphenidate)?

    No. Methylphenidates do not belong to the class of amphetamines, and immunoassays for amphetamines do not detect them. Furthermore, the half-life of methylphenidates is very short (~ 2 hours). To monitor compliance for methylphenidates, a quantitative LC-MS/MS test and critical-frozen specimen are required. Urine should be collected within 8 hours of dosing, and blood (serum/plasma) within 4 hours of dosing.
  • Will certain medications cause a positive screen for a drug/drug class?

    Yes.It is important to investigate the active components of any drug that a patient is prescribed or has otherwise administered when interpreting a positive drug test. There are dozens of different trade names and formulations of popular drugs that may contribute legitimately to a positive drug test. There are also some drugs that are recognized to cause analytical interference and may contribute to a false positive drug test. Examples of drugs that cause false positive results include cyclobenzaprine in tricyclic antidepressant immunoassay screens, and phentermine in amphetamine immunoassay screens. A complete pharmacy history, including non-prescription medication, is critical. Consult the laboratory for discussion of possible false positive drug test results.
  • Will an immunoassay screen (for benzodiazepine) detect clonazepam (Klonopin)?

    Not usually. Most benzodiazepine immunoassays do not detect therapeutic concentrations of clonazepam or its common metabolite, 7-amino clonazepam. LC-TOF screens, or quantitation by LC-MS/MS are the best methodologies at ARUP for verifying clonazepam compliance. High-resolution hybrid screen using LC-TOF (urine 2007479), LC-MS/MS benzodiazepine panel (urine 0090358, serum/plasma 0093300), or clonazepam (serum/plasma 0090055).
  • Will the immunoassay screens for opiates detect opioids like fentanyl, buprenorphine, meperidine, and tramadol?

    No. However, these drugs can be detected with the high-resolution hybrid screen or with quantitative LC-MS/MS in serum/plasma or urine. See test menu for ordering information.
  • What exactly is included in the opiate portion of the immunoassay screening panels ?

    The immunoassay screens for opiates detect (but not individually report) codeine, hydrocodone, hydromorphone, morphine and the heroin metabolite (6-acetylmorphine, or 6-AM, 6-MAM). In the reflex screens, oxycodone, oxymorphone are also reported as "opiates".
  • Can second-hand exposure to marijuana result in a positive urine test?

    It is unlikely for passive inhalation of marijuana smoke to result in a positive urine test. While second hand smoke is a source of drug exposure, the amount of drug that is absorbed is far less than the amount of drug absorbed after deliberate, intentional drug use. Concentrations of marijuana metabolites in urine observed after exposure to second hand marijuana smoke are usually below the cutoff of both the screening test (15 – 20 ng/mL) and urine confirmation/quantitation test (5 ng/mL). Exceptions may exist particularly if there was significant/constant exposure. Consult references below:
    - German/Dutch study involving passive cannabis exposure in a coffee shop: urine and blood
    - German study: blood
  • How many poppy seeds does one have to ingest to get a positive test result for morphine?

    Poppy seeds vary greatly in morphine content. Therefore, it is not appropriate to make a general statement about the actual amount of poppy seeds required to trigger a positive test result. Raw (uncooked) poppy seeds contain the highest amount of morphine. The federal government (SAMHSA) uses a positive cutoff of 2000 ng/mL to eliminate most of the positive results that are due to ingestion of poppy seed.
    The following article reports that up to 13,827 ng/mL of morphine was detected in urine after 150g of poppy seeds was ingested over a period of 3 weeks.
    - Multiple aspects of hair analysis for opiates: methodology, clinical and workplace populations, codeine, and poppy seed ingestion. 2005
    The following is a good review on the topic:
    - Poppy seed foods and opiate drug testing—where are we today? 2010
  • What qualifications are required to perform the point-of-care drug screen cup? Does one need to be an MT or CLS?

    The ARUP Drug Screen Cup is a CLIA-waived FDA-cleared point-of-care test device. It can be performed by technologists, technicians, as well as nonlaboratory personnel (minimum of high-school diploma required). For instance, a nurse or medical assistant in a physician’s office may perform the point-of-care drug screen using the urine testing cup. Alternatively, urine can be sent to a central lab where the specimen is transferred into the testing cup and results are recorded.
    Waived testing under CLIA requires the laboratory/facility to register the procedure and obtain a waived certificate. Requirements for proficiency testing, quality control procedures, and record keeping vary depending on the type of facility. If the CLIA-waived test is performed in a nonhospital setting, the responsibility for and management of testing should be through affiliation with a pathologist or laboratory director of a parent health care organization, or through a clinical consultant with comparable credentials (such as a registered med tech (MT) or a clinical laboratory scientist (CLS)).
  • Why is buprenorphine not included in the urine immunoassay screen?

    We do not include buprenorphine in any of our immunoassay screens (whether for the point-of-care cup or for the lab tests), because of concern over the performance of commercially available reagents for this target. We have observed higher than acceptable levels of false positives and negatives. If buprenorphine is prescribed to the patient, the best strategy at this time is to order the quantitative buprenorphine test by LC-MS/MS at the same time an immunoassay screen is ordered for the patients, or to order the high-resolution hybrid screen which specifically detects buprenorphine and many other opioids.
  • Will Ritalin and Adderall show up in a urine immunoassay screen?

    Yes, for Adderall. No, for Ritalin. Adderall contains d-amphetamine and should be detected by the amphetamine screens, provided that specimen is collected at an appropriate time after drug administration (please inquire if you need to discuss this further). Ritalin is methylphenidate and will not be detected unless the test for methylphenidate is specifically ordered.

    Selection of tests

  • How can I determine if a patient has been abstaining from marijuana?

    A good way to evaluate elimination of marijuana is to normalize results to creatinine, and compare results for specimens collected at least one week apart. If a person has abstained from new use of marijuana, normalized concentrations should decrease over time. For further details, consult the following references:

    - Schwilke EW, Gullberg RG, Darwin WD, Chiang CN, Cadet JL, Gorelick DA, Pope HG, Huestis MA. Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction. 2011 Mar;106(3):499-506.

    - Smith ML, Barnes AJ, Huestis MA. Identifying new cannabis use with urine creatinine-normalized THCCOOH concentrations and time intervals between specimen collections. J Anal Toxicol. 2009 May;33(4):185-9.
  • Which test should I use for monitoring of methylphenidates (Ritalin, Focalin)?

    To monitor compliance for methylphenidate or dexmethylphenidate, a quantitative LC-MS/MS test and critical-frozen specimen are required. Urine should be collected within 8 hours of dosing, and blood (serum/plasma) within 4 hours of dosing. Urine (2003115), and serum/plasma (2003114). These tests do not distinguish between d- and l- isomers of methylphenidate.
  • Which test should I use for monitoring clonazepam (Klonopin)?

    The high-resolution hybrid screen (urine, 2007479) is the best methodology at ARUP for verifying compliance to clonazepam as long as quantitative results are not clinical necessary. If quantitation is required, use the LC-MS/MS benzodiazepine panel (urine 0090358, serum/plasma 0093300), or clonazepam (serum/plasma 0090055).

    Testing strategy

  • When should a confirmation test be ordered?

    A confirmation test can be ordered when a screen result is inconsistent with the expectation. If screen results match expectations, it is not necessary to confirm every positive result or to perform broad-spectrum confirmatory testing, unless there are other concerns (such as adulteration of the specimen). Confirmation tests can be qualitative or quantitative, and typically use mass spectrometry preceded by chromatographic separation in order to provide a high level of specificity to compound identification.
  • When should a quantitative test be ordered?

    Quantitative drug tests are useful when (1) quantitative data are required to monitor patients longitudinally; (2) a pharmacokinetic or pharmacodynamic problem is suspected (serum/plasma specimens are required for this type of testing); (3) proportional relationships between compounds are used to distinguish drugs, drug metabolites, and possible pharmaceutical contaminants; and (4) to investigate specimen adulteration intended to mimic adherence to therapy (see McMillin et al., 2012 as an example: http://www.ncbi.nlm.nih.gov/pubmed/22337776.
  • I need a certain drug automatically quantified and confirmed after a screen, even if the screen is negative. How do I arrange that?

    Order a quantitation test specific for the prescribed drug at the same time you order a screen panel. Many clients order the quantitation test for opiates and oxycodone (0090364) together with the urine screen panel (0090453). Quantitation of benzodiazepines and individual opioids are also commonly ordered together with the screen. If you wish to confirm every analyte that was screened positive automatically AND confirm the prescribed drug even if screened negative, order the quantitation test for the prescribed drug in addition to the screen-reflex test (0092186). If the prescribed drug was positive by the screen, the additional test will be canceled automatically to avoid duplicate testing.
  • Is routine adulteration testing important for urine drug testing in pain management?

    No. Traditional drug abuse testing incorporates routine adulteration testing due to suspicions regarding donors trying to “beat” the drug test. Adulterants in traditional drug abuse testing may include specimen dilution, and additives such as nitrites or oxidants. However, in a pain management setting, the donor/patient is concerned about “passing” the drug test. Adulteration in a pain management population may involve the addition of drug (as powder or liquid) directly to urine specimens to mask the fact that the patient is not taking the drug as prescribed. This type of adulteration is best detected through targeted quantitative (confirmation) testing. Urine substitution is also a concern. Some substitutions can be detected by measuring creatinine or specific gravity. However, substitution with human urine (e.g. archived urine from the patient) cannot be detected by adulteration testing. When specimen adulteration is suspected, observed collections or blood testing is recommended. Adulteration of blood specimen is rare.

    Specimen

  • Can specimens be combined for drug testing?

    Yes. If more than one specimen is collected for an individual patient at the same time, those specimens can be combined to provide a larger testing volume. Mixing routine blood preservatives (such as EDTA and heparin) is not expected to interfere with drug testing.
  • When is urine a less preferred specimen type?

    When adulteration of the urine specimen is of concern, a blood specimen (serum or plasma) is often used. Also, a serum or plasma specimen is appropriate for patients on dialysis, for suspected cases of malabsorption (e.g. gastric bypass), and for evaluating other aspects of individual patient''s pharmacokinetics.
  • What are the major differences of using urine versus other specimens such as saliva and hair for drug screening?

    Urine is preferred because drugs concentrate in the urine over time, which extends the time over which a drug may be detected. Urine is also non-invasive and inexpensive to collect and test, in most cases. Urine is, however, susceptible to adulteration or substitution by the donor. In contrast, both saliva (oral fluid) and blood are observed collections, thus lowering the likelihood of specimen adulteration or substitution. Saliva concentrations and the time course for detection more closely approximate blood (including serum/plasma) than urine. Of concern, however, is that not all drugs are represented in saliva. For example, opiates and amphetamines are observed in saliva, but benzodiazepines and barbiturates are not. Blood is the preferred specimen for correlating signs and symptoms with drug concentrations in a real-time acute setting. Hair is useful for demonstrating chronic exposure/use. Each centimeter of head hair represents approximately 1 month of time. Sampling errors, external contamination of the hair sample, efficiency of drug deposition into the specific type/color of hair, and laboratory performance limitations may compromise utility of hair for drug testing.
  • When is plasma or serum a preferred specimen for drug screening or monitoring?

    A serum or plasma specimen is appropriate for patients on dialysis, for suspected cases of malabsorption (e.g. gastric bypass), and for evaluating other aspects of individual patient''s pharmacokinetics.
  • Can I use the urine in the point-of-care cup for confirmation by mass spectrometry?

    Yes, if you are using the testing cup supplied in the ARUP Drug Screen Kit. Transfer the urine from the cup into the tube included in the kit, and send to ARUP for quantitation/confirmation testing.
  • What can I use to QC the point-of-care ARUP Drug Screen cups?

    One option is to use the "Stat-Skreen with MDMA, OXY & BUP (low opiate controls)" (Cat#19001066) with the Negative Control (Cat#19700000) sold by Biochemical Diagnostics, Inc. (Edgewood, NY). Proficiency survey materials can be obtained from www.cap.org (Drug Monitoring for Pain Management DMPM).