Lab

Toxicology Screening

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Toxicology Screening, Urine Tox Screen, Urine Drug Screen

  • Indications
  1. Acute medical condition
    1. Altered Level of Consciousness
    2. Excited Delirium
    3. Unknown Ingestion
    4. Date Rape Drug suspected
  2. Medication Compliance
    1. Opioid, Benzodiazepine or other controlled substance prescription monitoring
    2. Chemical Dependency Rehabilitation
  3. Participation
    1. Employment (e.g. transportation licensing for commerical drivers, pilots)
    2. Military participation
    3. Sports participation
  • Precautions
  1. Urine toxicology utility has been markedly reduced by the growing use of synthetics
    1. Synthetic Cannabinoids
    2. Psychoactive Bath Salts
  2. 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
  3. 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
  1. 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
  1. Urine Temperature (within 4 minutes of voiding): 90 F (32.2 C) to 100 F (37.7 C)
  2. Urine pH: 4.5 to 8.5 (some facilities use pH 3.0-11.0)
  3. Urine Creatinine: 20 mg/dl or greater (otherwise artificially diluted)
  4. Nitrite concentration <500 mg/dl (<4.2 mmol/L)
  5. Sample size 30 ml or more
  • Protocol
  • Prevent urine sample tampering
  1. Remove outer clothing (jackets, sweatshirts, hat)
  2. Remove any items in urine collection area that could be used to tamper with sample (bleach, vinegar, soap, ammonia, salt)
  3. Remove any items from pockets
  4. Do not allow briefcases, backpacks, purses and other similar items in collection area
  5. Patient should wash and dry hands with liquid soap under observation
  6. Add bluing agent to toilet and turn off water to the testing area
  7. Observe the actual collection and use chain of custody forms to accompany the sample
  8. Consider split sample collections with tamper resistant containers
  • Protocol
  • Urine Drug Testing Frequency in controlled substance prescription monitoring
  1. 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
        1. Intoxication at visit
  2. Low risk of misuse
    1. Urine drug test every 6 to 12 months
  3. Moderate risk of misuse
    1. Urine drug test every 3 to 6 months
  4. High risk of misuse
    1. Urine drug test every 1 to 3 months
  5. References
    1. WSAMDG Guideline on Prescribing Opioids for Pain
      1. http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf
  • Labs
  1. Screening Basic Qualitative Urine Immunoassay (typically 5 Drug Class)
    1. Opioids
    2. Cannabinoids
    3. Cocaine
    4. Amphetamines
    5. Phencyclidine
  2. 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)
  1. Alcohol (Ethanol)
    1. Detection Positive: 3 to 10 hours
  2. 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
  3. 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
  1. Detection Direct: 5 hours
  2. Analytes (metabolites): Benzoylecgonine, Ecgonine methyl ester
  3. Detection Metabolites: 2-4 days (may persist as long as 8 days with heavy use)
  4. Causes: False Positive tests
    1. Coca leaf tea
    2. Topical Anesthetics containing Cocaine
  • Preparations
  • Stimulants - Bath Salts
  1. Not detected by routine Urine Drug Screening
  2. Liquid and gas chromatography-mass spectrometry may detect bath salts and other synthetics
    1. Not widely available, expensive and prolonged test turn-around time
  1. Positive: 1 to 3 days
  2. Detects Amphetamine at 500 ng/ml in Urine Drug Screen (and 250 ng/ml in confirmatory testing)
  3. Detects Methamphetamine at 250 ng/ml in Urine Drug Screen
  4. Decreased urine Test Sensitivity with large bicarbonate ingestions
  5. May also detect MDMA
  6. 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
  1. See Opioid Metabolism
  2. 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
        1. Methadone
        2. Buprenorphine
        3. Meperidine
        4. Tramadol
  3. 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
  4. 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)
  1. Detection
    1. Positive: 2 to 8 days (may persist as long as 14-28 days in some cases of chronic use)
  2. 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
  1. 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]
  2. Analytes
    1. 11-nor-9-carboxy-Tetrahydrocannabinol
  3. 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
  4. 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
  1. Methaqualone (Quaalude)
    1. Positive: 2 weeks
  2. Rohypnol
    1. Positive: 72 hours
  3. GHB
    1. Positive: 6-12 hours
  4. Soma
    1. Detected as Meprobamate (metabolite)
  • Causes
  • Adulterants that prevent drug detection in urine
  1. Acetic Acid (Vinegar)
    1. Decreases Test Sensitivity for Tetrahydrocannabinol (THC)
  2. Ammonia
    1. Masks detection of benzoylecgonine and Phencyclidine
  3. Benzalkonium chloride (Visine eye drops)
    1. Decreases Test Sensitivity for Tetrahydrocannabinol (THC)
  4. Diuretics with water intake
    1. Dilutes urine to undetectable substance concentrations
  5. Sodium Hypochlorite (Bleach)
    1. Masks immunoassay and may also breakdown metabolites for gas chromatography
  6. Glutaraldehyde (Urinaid, Clean-X)
    1. Decreases immunoassay Test Sensitivity for several substances
  7. Goldenseal (Hydrastis canadensis)
    1. Herbal Diuretic that dilutes urine and decreases immunoassay sensitivity to Amphetamines, THC
  8. Potassium Nitrite (Klear or Whizzies)
    1. Decreases immunoassay, gas chromatography, mass spectrometry Test Sensitivity
  9. Pyridium chlorochromate (Urine Luck, Instant Clean Add-it-ive)
    1. Oxidizing Agent that decreases immunoassay, gas chromatography, mass spectrometry sensitivity
  10. Powdered urine (Dry human urine residue)
    1. Substitutes a clean urine for the patient's urine
  11. Peroxide and Peroxidase (Stealth)
    1. Masks immunoassay for THC and Opioids
  12. Other agents used
    1. Niacin
  13. References
    1. Fu (2016) Adv Clin Chem 76:123-63 [PubMed]
  • Costs
  1. Typical screening immunoassay costs $128 ($62 to $308)
  2. Insurance coverage is variable