Drug Testing

Last Literature Review: December 2019 Last Update:

Medical Experts



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

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.

Which laboratory test is appropriate to determine whether a patient has been abstaining from marijuana?

Creatinine normalization may be useful to evaluate whether a patient has abstained from new use of marijuana. If a patient has abstained from new use of marijuana, the concentrations in urine of the creatinine-normalized delta-9-tetrahydrocannabinol (THC) metabolite, THC acid (THCA), should decrease over time. To demonstrate elimination of THCA (decreasing concentration) or new use of marijuana (increasing concentration of THCA), an appropriate testing interval is no more than once per week.

Many quantitative clinical assays for detection of THC and related metabolites (including ARUP’s) do not routinely include creatinine measurement. To determine a creatinine-normalized THC concentration, creatinine testing should be ordered or performed at the same time a urine specimen is collected for THC testing. It is best if the same creatinine and THC methods are utilized for serial samples collected from the same patient. To calculate a normalized concentration, use the following formula:

[THC (ng/mL) / creatinine (mg/dL)] x 100 = ng THC per mg creatinine

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?

The interpretation of results may be complicated by several factors, including timing of sample collection and drug impurities.  For more information about these challenges or for assistance with result interpretation, consider the following resources:

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.


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 TypeStrengthsLimitations

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


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

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.


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. 


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).


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 ClassExamples 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
MethadonePropoxyphene, antihistamines
OpiatesRifampicin, quinolones, ofloxacin, naloxone, levofloxacine, ofloxacine, pefloxacine, enoxacine, gatifloxacine, lomefloxacine, moxifloxacine, ciprofloxacine, norfloxacine
Phencyclidines Dextromethorphan, lamotrigine, venlafaxine
Cannabinoid (marijuana)Efavirenz, ibuprofen, naproxen, niflumic acid
Tricyclic antidepressantsCarbamazepine, 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 PanelsDrug Profile, Targeted by Tandem Mass Spectrometry and Enzyme Immunoassay, Urine; Drug Profile, Targeted with Interpretation by Tandem Mass Spectrometry and Enzyme Immunoassay, Urine; and Drug Profile, Screen with Reflex to Quantitation
Immunoassay Drug/ClassConfirmation Test(s)aDrug(s) and/or Metabolite(s) Included

Amphetamines (D/L Differentiation), Urine 2014043

Amphetamines, Urine, Quantitative 2010075

Amphetamine, methamphetamine, MDA, MDMA (Ecstasy), MDEA (Eve), phentermine
BarbituratesBarbiturates, Urine, Quantitative 2012213Butalbital, amobarbital, pentobarbital, secobarbital, phenobarbital
BenzodiazepinesBenzodiazepines, Urine, Quantitative 2008291Alprazolam, alpha-hydroxyalprazolam, chlordiazepoxide, clonazepam, 7-aminoclonazepam, diazepam, lorazepam, midazolam, alpha-hydroxymidazolam, nordiazepam, oxazepam, temazepam
BuprenorphineBuprenorphine and Metabolites, Urine, Quantitative 2010092Buprenorphine, norbuprenorphine, buprenorphine glucuronide, norbuprenorphine glucuronide, naloxone
CannabinoidsTHC Metabolite, Urine, Quantitative 009036911-nor-9-carboxy-tetrahydrocannabinol (THC)
Carisoprodol/meprobamateCarisoprodol and Meprobamate, Urine, Quantitative 2012219Carisoprodol, meprobamate
CocaineCocaine Metabolite, Urine, Quantitative 0090359Benzoylecgonine
Ethyl glucuronideEthyl Glucuronide and Ethyl Sulfate, Urine, Quantitative 2007909Ethyl glucuronide, ethyl sulfate
FentanylFentanyl and Metabolite, Urine, Quantitative 0092570Fentanyl, norfentanyl
GABA analoguesGabapentin, Urine 2012227
Pregabalin, Urine 2012229
Gabapentin, pregabalin
MeperidineMeperidine and Metabolite Quantitative, Urine 3000248Meperidine, normeperidine
MethadoneMethadone and Metabolite, Urine, Quantitative 0090362Methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)
Opiates/oxycodoneOpiates, Urine, Quantitative 0090364Codeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, hydromorphone, oxycodone, noroxycodone, oxymorphone, noroxymorphone
Phencyclidine (PCP)Phencyclidine (PCP), Urine, Quantitative 2010462PCP
TapentadolTapentadol, Urine, Quantitative 2003128Tapentadol
TramadolTramadol and Metabolites, Urine, Quantitative 2002736Tramadol, O-desmethyltramadol
ZolpidemZolpidem, Urine, Quantitative 2012319Zolpidem

aExtended panel includes confirmation testing, if needed.

GABA, gamma aminobutyric acid

Test Result Interpretation

Test results may be surprising not only when unexpected positive results are found, but also when expected positives are absent. Refer to the Urine Drug Testing (Unexpected Results) Algorithm for additional information on assessing unexpected results..

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 takenExpected drug was not taken recently
Unusual patient pharmacokinetics (eg, slow metabolizer)Unusual patient pharmacokinetics (eg, fast metabolizer)
Drug detected is a metaboliteSpecimen quality prevented detection (eg, dilute urine)
Drug detected is a pharmaceutical impurityTest not designed to detect drug of interest (eg, improper test choice, test limitations)
Drug was added to urine after collectionDrug metabolites not detected
Test limitations/errorsTest 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).

Sedative-Hypnotics Test Result Interpretation
Drug NameExample Trade Name(s)Reported Drug(s) and Metabolite(s) That Indicate Usea
AlprazolamXanaxAlprazolam, alpha-hydroxyalprazolam
BarbituratesbAmytalButalbital,c amobarbital,c pentobarbital,c phenobarbital,csecobarbital
CarisoprodolbSomaCarisoprodol,c meprobamatec
ChlordiazepoxideLibriumNordiazepam, oxazepam
ClorazepateTranxeneNordiazepam, oxazepam
ClonazepamClonopin, KlonopinClonazepam, 7-aminoclonazepam
DiazepamValium, ValreleaseDiazepam, nordiazepam, temazepam, oxazepam
MidazolamVersedMidazolam, alpha-hydroxymidazolam
TemazepamNormison, RestorilTemazepam
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 NameExample Trade Name(s)Reported Drug(s) and Metabolite(s) That Indicate Usea
BuprenorphineBuprenex, Suboxone, SubutexBuprenorphine, norbuprenorphine
CodeineTylenol-Codeine No. 3Codeine, morphine
FentanylActiq, Duragesic, FentoraFentanyl, norfentanyl
Heroinn/aMorphine, 6-acetylmorphine,b codeine
HydrocodoneAnexsia, Vicodin, LortabHydrocodone, norhydrocodone, hydromorphone
MeperidineDemerol, MeperganMeperidine metabolite (normeperidine)
MethadoneMethadoseMethadone,c EDDPd
MorphineAstromorph, Avinza, DepoDurMorphine, hydromorphone
NaloxoneNarcan, Evzio, Suboxone, ZubsolvNaloxone, noroxymorphone (same as nornaloxone)
OxycodoneOxycontin, PercocetOxycodone, noroxycodone, oxymorphone, noroxymorphone
OxymorphoneNumorphan, OpanaOxymorphone, noroxymorphone
TapentadolNucyntaTapentadol, tapentadol-O-sulfate
TramadolUltramTramadol,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 NameExample Trade NameReported Drug(s) and Metabolite(s) That Indicate Use
Cocainen/aCocaine,a benzoylecgonineb
Methamphetaminecn/aMethamphetamine, amphetamine
aMinimal detection or not detected by the IA.
bDetected by IA.
cListed drugs and metabolites may not all be present for each patient.
GABA Analogues Test Result Interpretation
Drug NameExample Trade NameReported Drug or Metabolite That Indicates Use
GabapentinGralise, NeurontinGabapentin
Marijuana, PCP Test Result Interpretation
Drug NameReported Drug or Metabolite That Indicates Use
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 Laboratory Tests

For a comprehensive list of ARUP drug testing options, refer to the Laboratory Test Directory.

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 Drug Profile, Targeted by Tandem Mass Spectrometry and Enzyme Immunoassay, Urine (2007479)

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

For additional information, refer to the Drug Profiles, Targeted by Mass Spectrometry and Enzyme Immunoassay Test Fact Sheet.

Does not provide interpretation of results; if interpretation is required, refer to Drug Profile, Targeted with Interpretation by Tandem Mass Spectrometry and Enzyme Immunoassay, Urine (2009288)

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

For additional information, refer to the Drug Profiles, Targeted by Mass Spectrometry and Enzyme Immunoassay Test Fact Sheet.

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


Serum/Plasma Tests

Use to monitor patient compliance

Provides quantitative results for confirmatory positive results

Confirmation Tests


Additional Resources