Toxicology Screening

See Also

Indications

Acute medical condition
Medication Compliance
1. Opioid, Benzodiazepine or other controlled substance prescription monitoring
2. Chemical Dependency Rehabilitation
Participation
1. Employment (e.g. transportation licensing for commerical drivers, pilots)
2. Military participation
3. Sports participation

Precautions

Urine toxicology utility has been markedly reduced by the growing use of synthetics
1. Synthetic Cannabinoids
2. Psychoactive Bath Salts
Urine toxicology misses many standard substances
1. Does not detect the most frequently used Benzodiazepines (Alprazolam, Clonazepam, Lorazepam)
2. Variable detection of MDMA (Ecstasy)
3. Does not detect semi-synthetic and synthetic Opioids
Positive drug screen does not exclude serious other causes for Altered Mental Status
1. Meningitis or Intracranial Hemorrhage may coexist with a positive Urine Drug Screen

Efficacy

Random urine drug testing may decrease Illicit Drug use in those on Chronic Opioid therapy
1. Manchikanti (2006) Pain Physician 9(2): 123-9 [PubMed]

Protocol
Assess validity of real urine sample

Urine Temperature (within 4 minutes of voiding): 90 F (32.2 C) to 100 F (37.7 C)
Urine pH: 4.5 to 8.5 (some facilities use pH 3.0-11.0)
Urine Creatinine: 20 mg/dl or greater (otherwise artificially diluted)
Nitrite concentration <500 mg/dl (<4.2 mmol/L)
Sample size 30 ml or more

Protocol
Prevent urine sample tampering

Remove outer clothing (jackets, sweatshirts, hat)
Remove any items in urine collection area that could be used to tamper with sample (bleach, vinegar, soap, ammonia, salt)
Remove any items from pockets
Do not allow briefcases, backpacks, purses and other similar items in collection area
Patient should wash and dry hands with liquid soap under observation
Add bluing agent to toilet and turn off water to the testing area
Observe the actual collection and use chain of custody forms to accompany the sample
Consider split sample collections with tamper resistant containers

Protocol
Urine Drug Testing Frequency in controlled substance prescription monitoring

Predictors of misuse
1. Mental health disorder
2. Substance Use Disorder
3. Prior Opioid misuse
4. Opioid dose >120 mg Morphine Equivalents
5. Lost prescriptions
6. Multiple requests for early refills
7. Opioid prescriptions from multiple physicians
8. Unauthorized dose increases
Low risk of misuse
1. Urine drug test every 6 to 12 months
Moderate risk of misuse
1. Urine drug test every 3 to 6 months
High risk of misuse
1. Urine drug test every 1 to 3 months
References
1. WSAMDG Guideline on Prescribing Opioids for Pain
  1. http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf

Labs

Screening Basic Qualitative Urine Immunoassay (typically 5 Drug Class)
Reference Lab Confirmatory testing (gas chromatography or high performance liquid chromatography)
1. Indicated for positive results and unexpected negative results
2. Specific immunoassay examples
  1. Synthetic and Semisynthetic Opioids (e.g. Methadone, Buprenorphine, Oxycodone, Fentanyl)
  2. Benzodiazepines not found on immunoassay (e.g. Alprazolam, Lorazepam, Clonazepam)
  3. Synthetic Cannabinoids (e.g. K2, Spice)
  4. Cathinones (bath salts)
  5. Hallucinogens (N-Bomb)

Preparations
Sedatives and Hypnotics

Alcohol (Ethanol)
1. Detection Positive: 3 to 10 hours
Barbiturates
1. Detection
  1. Short-Actings agents: 1-2 days
  2. Long-acting agents (e.g. Phenobarbital): 21 days
2. Causes: False Positive tests
  1. Ibuprofen
  2. Naproxen
Benzodiazepines
1. See Benzodiazepine Metabolism
2. Many hospital-based Urine Drug Screens only detect Oxazepam and its precursors (Diazepam, Librium)
  1. These Urine Drug Screens miss Alprazolam, Clonazepam, Lorazepam, Flunitrazepam (Rohypnol)
3. Detection (high doses may be detectable up to 6 weeks)
  1. Short-acting agents (e.g. Lorazepam, Alprazolam): 3-5 days
  2. Long acting agents (Clonazepam, Diazepam): 30 days
  3. Zolpidem (Ambien): 1 to 5 days
4. Analytes
  1. Alpha-hydroxyalprazolam
  2. 7-Aminoclonazepam
  3. Oxazepam
5. Causes: False Positive tests
  1. Oxaprozin (Daypro)
  2. Sertraline (Zoloft)

Preparations
Stimulants - Cocaine

Detection Direct: 5 hours
Analytes (metabolites): Benzoylecgonine, Ecgonine methyl ester
Detection Metabolites: 2-4 days (may persist as long as 8 days with heavy use)
Causes: False Positive tests
1. Coca leaf tea
2. Topical Anesthetics containing Cocaine

Preparations
Stimulants - Bath Salts

Not detected by routine Urine Drug Screening
Liquid and gas chromatography-mass spectrometry may detect bath salts and other synthetics
1. Not widely available, expensive and prolonged test turn-around time

Preparations
Stimulants - Amphetamine or Methamphetamine

Positive: 1 to 3 days
Detects Amphetamine at 500 ng/ml in Urine Drug Screen (and 250 ng/ml in confirmatory testing)
Detects Methamphetamine at 250 ng/ml in Urine Drug Screen
Decreased urine Test Sensitivity with large bicarbonate ingestions
May also detect MDMA
Causes: False Positive tests
1. Amantadine
2. Benzphetamine (Regimex)
3. Brompheniramine
4. Bupropion (Wellbutrin)
5. Chlorpromazine
6. Chloroquine
7. Desipramine
8. Doxepin
9. Fluoxetine (Prozac)
10. Labetalol
11. Levomethamphetamine (OTC nasal Decongestant sprays)
12. Methylphenidate (Ritalin)
13. MDMA
14. Phentermine
15. Phenylephrine
16. Phenylpropanolamine
17. Promethazine (Phenergan)
18. Pseudoephedrine
19. Ranitidine (Zantac)
20. Selegiline
21. Thioridazine
22. Trazodone
23. Trimethobenzamide (Tigan)
24. Trimipramine (Surmontil)
25. Venlafaxine (Effexor)
26. Vicks Inhaler

Preparations
Opioids

See Opioid Metabolism
Tests
1. Gas chromatography: Detects all Opioids
2. Enzyme linked assays:
  1. Reliably detects naturally occurring Opiates (Opioid subset)
    1. Morphine
    2. Codeine
    3. Morphine metabolites (Heroin)
  2. Misses semi-synthetic Opioids (structurally similar to Opiates)
    1. Hydrocodone
    2. Oxycodone
    3. Hydromorphone
    4. Oxymorphone
    5. Fentanyl
  3. Misses synthetic Opioids
Preparations
1. Codeine
  1. Detection Positive: 1 to 2 days
  2. May be detected as analytes: Morphine, Hydromorphone
2. Heroin (detected as Morphine on less specific testing)
  1. Detection Positive: 2-3 days
  2. Analytes are the same as Morphine
  3. Analytes specific to Heroin
    1. 6-monoacetylmorphine (short half life)
    2. Acetylated-Thebaine-4-Metabolite Glucuronide
3. Hydromorphone (Dilaudid)
  1. Detection Positive: 1 to 2 days (up to 4 days in some cases)
4. Methadone (Dolophine)
  1. Detection Positive: 3 to 4 days (up to 14 days in some cases)
  2. Analytes: 2-ethylidene-1,5-dimethyl-3, 3-Diphenylpyrrolidine
5. Propoxyphene (Darvon)
  1. Detection
    1. Direct: 6 hours
    2. Metabolites: 6 to 48 hours
6. Fentanyl
  1. Detection positive: 2 to 3 days (up to 4 days in some cases)
  2. Analytes: Norfentanyl
7. Hydrocodone (e.g. Vicodin)
  1. Dectection positive: 1 to 2 days
  2. May be detected as Hydromorphone (metabolite)
8. Oxycodone (e.g. Percocet)
  1. Detection positive: 1 to 1.5 days (up to 3 days for controlled release)
  2. Analytes: Noroxycodone, noroxymorphone, Oxycodone, oxymorphone
9. Oxymorphone (Opana)
  1. Detection positive: 1.5 to 2.5 days (up to 4 days for controlled release)
  2. Analytes: Noroxymorphone
10. Morphine
  1. Detection Positive: 2-3 days
  2. Analytes: Codeine, Hydromorphone
11. Tapentadol (Nucynta)
  1. Detection Positive: 1 to 5 days
  2. Analytes: Tapentadol O-Sulfate
12. Tramadol
  1. Detection Positive: 2-4 days
  2. Analytes: Nortramadol
13. Buprenorphine (by specific reference testing)
  1. Detection at up to 11 days
  2. Analytes include Norbuprenorphine
False Positives
1. Chlorpromazine (Methadone)
2. Clomipramine (Methadone)
3. Dextromethorphan (Codeine or Morphine)
4. Diphenhydramine (Methadone)
5. Doxylamine (Methadone)
6. Fluoroquinolones (esp. Ofloxacin, Levofloxacin positive for Codeine or Morphine)
7. Poppy seeds (requires very high concentration, unlikely to occur with typical food intake)
  1. Samano (2015) J Anal Toxicol 39(8): 655-61 [PubMed]
8. Quetiapine (Methadone)
9. Quinine (Codeine or Morphine)
10. Quinolones
11. Rifampin (Codeine or Morphine)
12. Thioridazine (Methadone)
13. Verapamil (Methadone)

Preparations
Hallucinogenics - PCP (Phencyclidine)

Detection
1. Positive: 2 to 8 days (may persist as long as 14-28 days in some cases of chronic use)
Causes: False Positive tests
1. Dextromethorphan
2. Diphenhydramine
3. Doxylamine
4. Ibuprofen
5. Imipramine
6. Ketamine
7. Meperidine (Demerol)
8. Synthetic Cathinones (Bath Salts)
9. Thioridazine
10. Tramadol
11. Venlafaxine

Preparations
Marijuana (THC metabolite, Cannabinoids)

General
1. Marijuana is lipophilic and is detectable for long periods after last use
2. Synthetic Marijuanas are not positive on Urine Drug Screens
3. Second hand Marijuana smoke does not cause a positive result (50 ng/ml or more)
  1. Positive test would require extreme exposures at high room concentrations
  2. Cone (2015) J Anal Toxicol 39(1): 1-12 [PubMed]
Analytes
1. 11-nor-9-carboxy-Tetrahydrocannabinol
Detection
1. Positive Urine
  1. Single use: 2 days (up to 7 days)
  2. Use 3-4 times per week: 7 days (up to 14 days)
  3. Used Daily: 2 to 4 weeks
  4. Long-term, heavy use: 4-6 weeks (up to 12 weeks)
2. Positive Blood: 8 hours
Causes: False Positive tests
1. Dronabinol (Marinol)
2. Cannabidiol (CBD) if impure (e.g. trace amounts of THC)
3. NSAIDS (especially Ibuprofen, Naproxen, Sulindac)
4. Hemp containing foods
5. Proton Pump Inhibitors (e.g. Pantoprazole)
6. Efavirenz (Sustiva)

Preparations
Miscellaneous Agents

Methaqualone (Quaalude)
1. Positive: 2 weeks
Rohypnol
1. Positive: 72 hours
GHB
1. Positive: 6-12 hours
Soma
1. Detected as Meprobamate (metabolite)

Causes
Adulterants that prevent drug detection in urine

Acetic Acid (Vinegar)
1. Decreases Test Sensitivity for Tetrahydrocannabinol (THC)
Ammonia
1. Masks detection of benzoylecgonine and Phencyclidine
Benzalkonium chloride (Visine eye drops)
1. Decreases Test Sensitivity for Tetrahydrocannabinol (THC)
Diuretics with water intake
1. Dilutes urine to undetectable substance concentrations
Sodium Hypochlorite (Bleach)
1. Masks immunoassay and may also breakdown metabolites for gas chromatography
Glutaraldehyde (Urinaid, Clean-X)
1. Decreases immunoassay Test Sensitivity for several substances
Goldenseal (Hydrastis canadensis)
1. Herbal Diuretic that dilutes urine and decreases immunoassay sensitivity to Amphetamines, THC
Potassium Nitrite (Klear or Whizzies)
1. Decreases immunoassay, gas chromatography, mass spectrometry Test Sensitivity
Pyridium chlorochromate (Urine Luck, Instant Clean Add-it-ive)
1. Oxidizing Agent that decreases immunoassay, gas chromatography, mass spectrometry sensitivity
Powdered urine (Dry human urine residue)
1. Substitutes a clean urine for the patient's urine
Peroxide and Peroxidase (Stealth)
1. Masks immunoassay for THC and Opioids
Other agents used
1. Niacin
References
1. Fu (2016) Adv Clin Chem 76:123-63 [PubMed]

Costs

Typical screening immunoassay costs $128 ($62 to $308)
Insurance coverage is variable

Resources

Clinical Drug Testing in Primary Care
1. https://www.drugsandalcohol.ie/19456/1/Tap_32_Clinical_Drug_Testing_in_Primary_Care..pdf

References

(2014) PL Detail-Document, Urine Drug Testing, Prescriber's Letter
Jaffee (2007) J Subst Abuse Treat 33(1): 33-42 [PubMed]
Kale (2019) Am Fam Physician 99(1):33-9 [PubMed]
Moeller (2008) Mayo Clin Proc 83(1): 66-76 [PubMed]
Smith (2016) Clin Lab Med 36(4):663-71 [PubMed]
Standridge (2010) Am Fam Physician 81(5): 635-40 [PubMed]