Drug Testing

Many substances that are prescribed for pain management and other legitimate indications are found to be taken incorrectly (either inadvertently or purposefully), shared, sold, or otherwise misdirected. In addition, many substances are available for illicit use, including prescription substances (eg, opioids, Adderall, Xanax) and nonprescription drugs (eg, heroin, methamphetamines).

To ensure safe and effective therapy, current practice guidelines recommend monitoring patients for adherence to prescribed medications and abstinence from nonprescribed drugs through periodic drug tests.  However, drug testing strategies and testing methods are not standardized, which adds challenges to the selection of the right test, collection of the appropriate specimen, and interpretation of test results.

Quick Answers for Clinicians

Which specimens are preferred for drug detection testing?

Urine is preferred because its collection is noninvasive and inexpensive, and drugs and their metabolites tend to concentrate in the urine over time. Saliva (oral fluid) is also noninvasive to collect but is associated with higher costs. Drug concentrations and the time course for detection in saliva more closely approximate concentrations and the detection window in blood than in urine. However, not all drugs are detectable in saliva, and both urine and saliva are susceptible to adulteration or substitution by the donor.  Blood (serum or plasma) is the preferred specimen for correlating signs and symptoms with drug concentrations in a real-time acute setting. Blood collection is an observed procedure, which lowers the likelihood of specimen adulteration or substitution. Blood specimens are also appropriate for patients on dialysis, for suspected cases of malabsorption (eg, gastric bypass), and for evaluating other aspects of an individual patient’s pharmacokinetics. Hair specimens, meconium, and umbilical cord tissue are useful for demonstrating chronic exposure/use.

When should confirmation testing be performed?

A confirmation test should be considered when a screen result is inconsistent with the expectation (eg, patient history) and when that result will impact patient care decisions. If screen results match expectations, it is not necessary to confirm results (positive or negative) or to perform other, secondary testing. Confirmation testing should also be considered if quantitative results are required to interpret the result. Most confirmation tests produce quantitative results, which are useful when evaluating abnormal patterns of results (eg, no metabolites present, an unexpected pattern of metabolites), or to verify elimination kinetics.

How long can a drug be detected after use?

The duration of time for which a drug can be detected is based on the following:

  • The pharmacokinetic properties of the drug itself
  • The metabolism and elimination abilities of patients
  • The dose and frequency of dosing
  • Detection limits of the test utilized
  • The quality of the specimen being tested

Most drugs are detected in urine for 24-48 hours after the last use. Some drugs are detected for shorter durations (eg, methylphenidate, some benzodiazepines) and others for much longer (eg, methadone, marijuana). Contact the laboratory for estimates on detection periods for a specific drug, or consult the Drug Plasma Half-Life and Urine Detection Window chart.

Could cannabidiol (CBD) usage cause a positive test result for tetrahydrocannabinol (THC)?

Cannabidiol (CBD) usage could possibly result in a positive tetrahydrocannabinol (THC) result, depending on the CBD product’s purity. Most CBD products are unregulated and could contain more THC than claimed on the label.  A small amount of THC in a CBD product could also accumulate in the body if the CBD product is used frequently. CBD does not cross-react with the urine immunoassay (IA) used by ARUP Laboratories for the detection of cannabis. 

Quantitative urine THC metabolite testing may help with the interpretation of an unexpected positive cannabis IA.

Can certain medications cause a positive screen result for a drug or drug class?

Yes. It is important to investigate the active components of any drug that a patient is prescribed or has otherwise been 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. For example, cyclobenzaprine can cause false-positive results in tricyclic antidepressant immunoassay (IA) screens, and phentermine can cause false-positive results in amphetamine IA screens (refer to the table, Compounds That May Produce False-Positive IA Screen Results, for more examples).

Can poppy seed consumption cause a positive urine opiate drug test?

Yes. Poppy seeds contain morphine and codeine. Ingesting large amounts of poppy seeds or products that contain poppy seeds (eg, cake, bagels, salad dressing) can cause a positive urine opiate test result. In order to eliminate most of the positive test results that are due to poppy seed consumption, the Substance Abuse and Mental Health Services Administration (SAMHSA) considers 2,000 ng/mL the positive cutoff for urine testing performed by immunoassay or definitive methods.  Patients should abstain from consuming poppy seeds for 3 days prior to a urine drug test. Positive results would also be expected with other matrices (eg, blood) after poppy seed consumption.

What is the difference between an opiate and an opioid, and why is this difference important when considering drug testing?

The words “opioid” and “opiate” are often used interchangeably. There are, however, subtle but important differences between them. “Opiates” are chemical compounds extracted or refined from natural plant matter; examples of opiates include morphine and codeine. Note that opiates are also opioids. The term “opioids” refers to all natural, synthetic, or semisynthetic chemical compounds that interact with opioid receptors in the body and brain. Examples include hydrocodone, oxycodone, and methadone. 

Where can I find interpretation assistance?
Which testing algorithms are related to this topic?

Specimen Selection and Timing of Collection

Refer to the ARUP Drug Plasma Half-Life and Urine Detection Window chart for specific testing information, including plasma half-life, urine detection windows, drug metabolites, and common trade and street names.

Specimens

Urine and blood specimen (serum or plasma) tests are available to detect most drugs commonly prescribed for pain management and other legitimate indications, as well as many illicit substances. Urine is typically preferred for adherence and drug exposure testing; serum or plasma is an acceptable alternative.  There is no evidence that drug testing in alternate specimens (eg, hair, saliva) is more effective than urine testing for monitoring adherence, such as in the management of patients with chronic noncancer pain (CNCP). 

Specimen Selection for Detection of Prescribed or Illicit Substances
Specimen Type Strengths Limitations

Urine

Typically preferred matrix for adherence and drug exposure testing 

Longer window of drug detection than in blood

Adequate specimen volume for drug screening and confirmation

Drug markers (parent drug or metabolites) are present in high concentrations

High risk of adulteration of sample by patient to avoid detection of noncompliance 

Observed specimen collection generally not performed 

Dilution varies (as indicated by creatinine concentrations), making false-negative results possible

Blood

Collection is observed (lower likelihood of specimen adulteration or substitution)

Useful for:

  • Patients on dialysis and patients who produce very dilute urine
  • Correlating symptoms or dose with drug concentration
  • Suspected cases of malabsorption (eg, gastric bypass)
  • Evaluating other aspects of patient’s pharmacokinetics

Collection is invasive and requires a phlebotomist

Saliva

Collection is noninvasive

Concentration and time course for detection in saliva more closely approximate concentrations and detection window in blood (an advantage over urine testing)

Currently not performed at ARUP Laboratories

Limited number of drugs detectable in saliva (eg, most opioids and amphetamines are observed in saliva, but most benzodiazepines are not)

Timing of Collection

Specimens should be collected for drug testing based on the clinical scenario and routine practices. For example, specimens may be collected for testing when qualifying patients for chronic therapy with opioids or other controlled substances, enrolling patients in substance misuse disorder programs, in situations when aberrant drug behavior is suspected, and in patients who are pregnant. This testing is intended to confirm the presence of prescribed medications that are detected by the test and to detect the presence of illicit and nonprescribed drugs.  

Commonly Used Testing Strategy (Screening and Definitive Testing)

Testing approaches are unique in terms of performance characteristics, and the best strategy for testing should align with the goals of testing. Test choices include screen only, screen and definitive confirmation (for positive results), and direct, definitive, targeted testing. The last is typically performed using mass spectrometry (MS) technology and may be quantitative or qualitative.

Initial Drug Testing Methodologies

Initial drug testing methodologies include point-of-care (POC) screening devices (eg, urine cups), laboratory immunoassays (IAs), and MS technologies.

Immunoassays

Screening by IA is a common methodology for detecting drug presence and may be qualitative or semiquantitative. IAs have several advantages as first-line screening tests, including ease of use, fast turnaround time, and lower costs; however, IAs can produce false-positive and false-negative results. 

Opiates

Most available IAs do not readily detect semisynthetic opioids (oxycodone, hydrocodone, and their metabolites) and synthetic opioids (eg, fentanyl, methadone, meperidine, tramadol). ARUP Laboratories’ IA screen for opiates includes an IA designed to detect oxycodone and its metabolites. ARUP also offers separate IA screens for synthetic opioids (eg, fentanyl, methadone, tramadol, meperidine, tapentadol) and semisynthetic opioids (eg, buprenorphine).

Benzodiazepines

A large number of drugs belong to the benzodiazepines group, and an assay’s ability to detect them varies based on assay formulation and cutoff limit. Most benzodiazepines are metabolized and conjugated before elimination through urine. Therefore, the IA’s ability to detect respective metabolites also contributes to its apparent sensitivity to detect certain drugs. Most IAs would not detect designer benzodiazepines.

Amphetamines and Methamphetamines

Urine IAs are designed to detect the d-isomer (psychoactive compound) of amphetamine and methamphetamine. Nevertheless, the IAs mostly react poorly to other synthetic central nervous system (CNS) stimulants, including phentermine (moderate sensitivity), methylphenidate, methylenedioxyethylamphetamine (MDEA), methylenedioxymethamphetamine (MDMA), and methylenedioxyamphetamine (MDA). ARUP Laboratories’ IA for urine amphetamines includes two components to detect certain synthetic CNS stimulants (MDEA, MDMA, MDA) and amphetamine and methamphetamine. The IA for amphetamines and methamphetamines also often produces high false-positive result rates.  Literature has reported various cases of false positivity due to different substances (refer to the table, Compounds That May Produce False-Positive IA Screen Results). It is recommended that all IA screen results be confirmed by a definitive methodology (gas chromatography [GC], or liquid chromatography-tandem MS [LC/MS/MS]) if a clinical decision is to be made on the basis of the drug testing results.

False-Positive Immunoassay Results

Many different compounds can contribute to false-positive immunoassay screen results. The table below provides examples.

Compounds That May Produce False-Positive IA Screen Results
Drug Class Examples of Compounds
Amphetamines    ,    ,     Phentermine, bupropion, trazodone (m-CPP), pseudoephedrine, ephedrine, benzphetamine, mephentermine, phenylpropanolamine, phenmetrazine, tranylcypromine, selegiline, chlorpromazine, Vicks nasal inhaler, desipramine, dimethylamylamine, promethazine, ofloxacin, metformin, mexiletine, metoprolol, labetalol, ranitidine, fenofibric acid, chloroquine, hydroxychloroquine, fluoroquinolones
Barbiturates  Ibuprofen, naproxen
Benzodiazepines  Oxaprozin, sertraline, efavirenz
Methadone Propoxyphene, antihistamines
Opiates Rifampicin, quinolones, ofloxacin, naloxone, levofloxacine, ofloxacine, pefloxacine, enoxacine, gatifloxacine, lomefloxacine, moxifloxacine, ciprofloxacine, norfloxacine
Phencyclidines  Dextromethorphan, lamotrigine, venlafaxine
Cannabinoid (marijuana) Efavirenz, ibuprofen, naproxen, niflumic acid
Tricyclic antidepressants Carbamazepine, cyclobenzaprine, quetiapine
Sources: Johnson-Davis, 2016 ; Leclercq, 2019 ; Colby, 2019 ; Snozek, 2018 ; Gomila, 2017 ; Queseda, 2015 ; Marin, 2015 ; Liu, 2014 ; Baron, 2011 ; Vorce, 2011 ; Reidy, 2011 ; Curtin, 2012 ; Siff, 1988 ; Fraser, 1998 ; Rengarajan, 2013 Saitman, 2014 
 

Definitive Testing

First-line definitive testing (qualitative or quantitative) is preferred for monitoring the use of relevant over-the-counter medications, prescribed and nonprescribed drugs, and illicit substances, when the service requirements for testing are well aligned with clinical needs. 

Definitive testing is also recommended for any IA (laboratory based or POC) result that is not consistent with the clinical expectations, and for opiates/oxycodone and/or benzodiazepines (regardless of the screen result) if the patient is prescribed those drugs. 

Targeted tests for specific drugs or drug classes are available as individually orderable tests that are useful for confirming results obtained at the client site or when only select drugs or drug classes are of interest.

Quantitative vs Qualitative Testing

Quantitative definitive urine testing is not more useful at detecting outcomes in a clinical context compared with qualitative definitive urine testing; quantitative definitive urine testing should not be used to evaluate dosage of administered drug or adherence to a prescribed dosage regimen.  Quantitative definitive urine testing can be used to:

  • Identify variant drug metabolism
  • Detect pharmaceutical impurities
  • Detect metabolism through minor routes 

The following testing guide for ARUP Laboratories' drug panels includes IA drug/class, confirmation test name and number, and drugs/metabolites included in the test.

Testing Guide for ARUP Laboratories' Drug Panels

Pain Management Drug Panel by High-Resolution Time-of-Flight or Tandem Mass Spectrometry and Enzyme Immunoassay, Urine; Pain Management Drug Screen with Interpretation by High-Resolution Time-of-Flight or Tandem Mass Spectrometry and Enzyme Immunoassay, Urine; and Pain Management Panel, Screen with Reflex to Quantitation

Immunoassay Drug/Class Confirmation Test(s)a Drug(s) and/or Metabolite(s) Included

Amphetamines

Amphetamines (D/L Differentiation), Urine 2014043

Amphetamines, Urine, Quantitative 2010075

Amphetamine, methamphetamine, MDA, MDMA (Ecstasy), MDEA (Eve), phentermine

Barbiturates

Barbiturates, Urine, Quantitative 2012213

Butalbital, amobarbital, pentobarbital, secobarbital, phenobarbital

Benzodiazepines

Benzodiazepines, Urine, Quantitative  2008291

Alprazolam, alpha-hydroxyalprazolam, chlordiazepoxide, clonazepam, 7-aminoclonazepam, diazepam, lorazepam, midazolam, alpha-hydroxymidazolam, nordiazepam, oxazepam, temazepam

Buprenorphine

Buprenorphine and Metabolites, Urine, Quantitative 2010092

Buprenorphine, norbuprenorphine, buprenorphine glucuronide, norbuprenorphine glucuronide, naloxone

Cannabinoids

THC Metabolite, Urine, Quantitative 0090369

11-nor-9-carboxy-tetrahydrocannabinol (THC)

Carisoprodol/meprobamate

Carisoprodol and Meprobamate, Urine, Quantitative 2012219

Carisoprodol, meprobamate

Cocaine

Cocaine Metabolite, Urine, Quantitative 0090359

Benzoylecgonine

Ethyl glucuronide

Ethyl Glucuronide and Ethyl Sulfate, Urine, Quantitative 2007909

Ethyl glucuronide, ethyl sulfate

Fentanyl

Fentanyl and Metabolite, Urine, Quantitative 0092570

Fentanyl, norfentanyl

Meperidine

Meperidine and Metabolite Quantitative, Urine 3000248

Meperidine, normeperidine

Methadone

Methadone and Metabolite, Urine, Quantitative 0090362

Methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)

Opiates/oxycodone

Opiates, Urine, Quantitative 0090364

Codeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, hydromorphone, oxycodone, noroxycodone, oxymorphone, noroxymorphone

Phencyclidine (PCP)

Phencyclidine (PCP), Urine, Quantitative 2010462

PCP

Propoxyphene

Propoxyphene and Metabolite, Urine, Quantitative 2010468

Propoxyphene, norpropoxyphene (qualitative only)

Tapentadol

Tapentadol and Metabolite, Urine, Quantitative 2003128

Tapentadol, tapentadol glucuronide, tapentadol-O-sulfate (qualitative only), N-desmethyltapentadol (qualitative only)

Tramadol

Tramadol and Metabolites, Urine, Quantitative 2002736

Tramadol, O-desmethyltramadol

Zolpidem

Zolpidem, Urine, Quantitative 2012319

Zolpidem

aExtended panel includes confirmation testing, if needed.

Test Result Interpretation

Testing results may be surprising not only when unexpected positive results are found, but also when expected positives are absent. ARUP Consult algorithms for unexpected positive and negative results can help clinicians investigate discrepant results. Refer to the ARUP Drug Testing Algorithm and the ARUP Drug Testing (Unexpected Results) Algorithm.

Resolving Unexpected Test Results
Presence of Unexpected Drug (Unexpected Positive Result) Absence of Expected Drug (Unexpected Negative Result)

Unexpected drug (illicit or provided by other prescriber) was taken

Expected drug was not taken recently

Unusual patient pharmacokinetics (eg, slow metabolizer)

Unusual patient pharmacokinetics (eg, fast metabolizer)

Drug detected is a metabolite

Specimen quality prevented detection (eg, dilute urine)

Drug detected is a pharmaceutical impurity

Test not designed to detect drug of interest (eg, improper test choice, test limitations)

Drug was added to urine after collection

Drug metabolites not detected

Test limitations/errors

Test limitations/errors

Specimen mix-up (intentional or accidental)

Specimen mix-up (intentional or accidental)

Source: McMillin, 2013 

Opioid and Benzodiazepine Metabolic Pathways

Detecting the presence or absence of drug metabolites can be challenging. Refer to the following metabolic pathways to understand how select opioids and benzodiazepines are metabolized.

Opioid Metabolic Pathway

Graphic of opiates and metabolites, including poppy seeds and heroin. Oxycodone has its own metabolite pathway.

Benzodiazepine Metabolic Pathway

Graphic of Benzodiazepine metabolic pathways. One metabolite can indicate several different benzodiazepines.

ARUP Laboratories' Drug Hybrid Detection Testing and Interpretation

ARUP employs two drug detection techniques, MS and IA, in its drug hybrid tests.

The following tables include interpretive information for the drugs/drug classes reported in ARUP Laboratories' drug hybrid tests (drug panel and drug screen with interpretation). Drugs detected by IA are indicated with a footnote; all other drugs are detected by MS. MS is used to qualitatively detect drugs and metabolites, whereas IA is used for a few drugs/drug classes based on the excellent analytical performance of the IA (eg, for marijuana metabolites) or the low positivity rate of the associated drug (eg, PCP, propoxyphene).

Sedative-Hypnotics Test Result Interpretation
Drug Name Example Trade Name(s) Reported Drug(s) and Metabolite(s) That Indicate Usea

Alprazolam

Xanax

Alprazolam, alpha-hydroxyalprazolam

Barbituratesb

Amytal

Butalbital,c amobarbital,c pentobarbital,c phenobarbital,secobarbital

Carisoprodolb

Soma

Carisoprodol,c meprobamatec

Chlordiazepoxide

Librium

Nordiazepam, oxazepam

Clorazepate

Tranxene

Nordiazepam, oxazepam

Clonazepam

Clonopin, Klonopin

Clonazepam, 7-aminoclonazepam

Diazepam

Valium, Valrelease

Diazepam, nordiazepam, temazepam, oxazepam

Lorazepam

Ativan

Lorazepam

Midazolam

Versed

Midazolam

Oxazepam

Serax

Oxazepam

Temazepam

Normison, Restoril

Temazepam

Zolpidem

Ambien

Zolpidem

aListed drugs and metabolites may not all be present for each patient​.
bDetected by IA.
cListed compounds are not individually identified. Total absorbencies for all detected compounds are used to report presence or absence.

 

Opioids Test Result Interpretation
Drug Name Example Trade Name(s) Reported Drug(s) and Metabolite(s) That Indicate Usea

Buprenorphine

Buprenex, Suboxone, Subutex

Buprenorphine, norbuprenorphine

Codeine

Tylenol-Codeine No. 3

Codeine, morphine

Fentanyl

Actiq, Duragesic, Fentora

Fentanyl, norfentanyl

Heroin

n/a

Morphine, 6-acetylmorphine,b codeine

Hydrocodone

Anexsia, Vicodin, Lortab

Hydrocodone, norhydrocodone, hydromorphone

Hydromorphone

Dilaudid

Hydromorphone

Meperidine

Demerol, Mepergan

Meperidine metabolite (normeperidine)

Methadone

Methadose

Methadone,c EDDPd

Morphine

Astromorph, Avinza, DepoDur

Morphine, hydromorphone

Oxycodone

Oxycontin, Percocet

Oxycodone, noroxycodone, oxymorphone, noroxymorphone

Oxymorphone

Numorphan, Opana

Oxymorphone, noroxymorphone

Propoxyphene

Darvon

Propoxyphene,c norpropoxyphenec

Tapentadol

Nucynta

Tapentadol, tapentadol-O-sulfate

Tramadol

Ultram

Tramadol,c O-desmethyl-tramadol,c N-desmethyl-tramadold

aListed drugs and metabolites may not all be present for each patient​.
bPresence required to accurately identify heroin use.
cDetected by IA.
dMinimal detection or not detected by the IA.

n/a, not applicable

Stimulants Test Result Interpretation

Drug Name Example Trade Name Reported Drug(s) and Metabolite(s) That Indicate Use

Amphetamine

Adderall

Amphetamine

Cocaine

n/a

Cocaine,a benzoylecgonineb

MDMAc

Ecstasy

MDMA, MDA

MDEAc

Eve

MDEA, MDA

MDAc

n/a

MDA

Methamphetaminec

n/a

Methamphetamine, amphetamine

Methylphenidate

Ritalin

Methylphenidate

Phentermine

Adipex-P

Phentermine

aMinimal detection or not detected by the IA.
bDetected by IA.
cListed drugs and metabolites may not all be present for each patient.

 

Marijuana, PCP Test Result Interpretation
Drug Name Reported Drug or Metabolite That Indicates Use

Marijuana

9-carboxy-tetrahydrocannabinola

PCP

PCPa

aDetected by IA.

Additional Resources

ARUP Laboratories offers several options to further assist clients in interpreting and understanding test results.  

  • Toxicologist review
  • 24/7 on-call service
  • Medical director assistance in the selection of tests and interpretation of results
  • Free CME, SAM, and CEU video lectures

Contact Client Services for information.

ARUP Lab Tests

Access a comprehensive list of ARUP drug testing options at www.aruplab.com. Targeted tests for specific drugs or drug classes are available as individually orderable tests that are useful for confirming results obtained at the client site or when select drugs or drug classes are of interest. Enhanced report links provide access to samples of the available enhanced reports. For example interfaced reports, please contact Client Services.

Urine Tests

Results indicate whether findings are consistent or inconsistent with supplied medication information

If medication information is not available or interpretation is not necessary, consider Pain Management Drug Panel by High-Resolution Time-of-Flight or Tandem Mass Spectrometry and Enzyme Immunoassay, Urine (2007479)

Secondary testing is generally not indicated but is available if confirmation or quantitation is desired

Does not provide interpretation of results; if interpretation is required, refer to Pain Management Drug Screen with Interpretation by High-Resolution Time-of-Flight or Tandem Mass Spectrometry and Enzyme Immunoassay, Urine (2009288)

Secondary testing is generally not indicated but is available if confirmation or quantitation is desired

Use for general testing in contexts of compliance and/or abuse

Provides quantitative results for confirmatory positive results

Use for general testing in contexts of compliance and/or abuse

Provides quantitative results for confirmatory positive results

 

Screen only

For follow-up of presumptive result, confirmatory testing by MS is recommended

Serum/Plasma Tests

Monitor patient compliance

Provides quantitative results for confirmatory positive results

Confirmation Tests

Medical Experts

Contributor
Contributor

McMillin

Gwendolyn A. McMillin, PhD
Professor of Clinical Pathology, University of Utah
Scientific Director, Mass Spectrometry Platform; Medical Director, Clinical Toxicology and Pharmacogenomics, ARUP Laboratories
Contributor

Yang

Yifei Yang, PhD, DABCC
Assistant Professor of Clinical Pathology, University of Utah
Medical Director, Toxicology, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®