Essentials for physicians and health care professionals ordering and interpreting urinary screens for drugs of abuse. Dr. Edward Randell
Disclosure of Potential for Conflict of Interest FINANCIAL DISCLOSURE Grants/Research Support: CIHR and others. Speakers Bureau/Honoraria: None Consulting Fees: None Other: Employee of Memorial University
Learning Objectives • Describe why urine is the preferred sample for drug of abuse screening • Describe common interfering substances • Identify factors to consider when interpreting positive and negative drug screens • Describe the strengths and limitations of common techniques used for urine drug screening
Why are UDS important to clinical practice? • Can identify more non-adherent patients than monitoring behavior and self-reporting alone • Identify new or recurrent drug misuse • Support clinical decisions • Assist diagnosis • Deterrent and provide objective evidence of abstinence in high risk patients
Why is interpreting UDS correctly important? • UDS screen interpretation carries significant potential for harm if done incorrectly • False accusations of drug abuse or diversion based on misinterpretation of UDS results carry potential medicolegal consequences. Health care professionals who effectively employ UDS have a good understanding of the pharmacology of commonly encountered drugs and work closely with lab professionals when ordering and interpreting these tests
Drug Screens Amphetamines and Methamphetamine Common Drug of Opiates Abuse Benzodiazepines Cocaine Barbiturates Methadone Phencyclidine Marijuana Oxycodone
A 40 years old female receiving Oxycodone, presents to a pain clinic for routine follow-up visit. A random urine drug screen is done by immunoassay and she tests positive for Marijuana (cannabinoids positive). When asked, she admits “I only smoked two puffs five days ago”. Fact or Myth? Introduction Check out discuss of similar case at: http://paindr.com/two-puffs-too-bad-demystifying- marijuana-urine-testing/
Quiz: 7 UDS questions What is detected in the urine following: 1. Acetaminophen/Codeine administration 2. Morphine administration 3. Heroine use 4. Poppy seed consumption 5. 2 nd hand exposure to Marijuana smoke 6. Explain a negative drug screen result for a patient on chronic opioid therapy… 7. On receiving a negative result on an opiate screen for a patient you prescribed hydromorphone you would…
• To determine level of UDS interpretative knowledge of physicians who use UDS to monitor adherence on chronic opioid therapy • 7 question survey given to 114 physicians 77 who use UDS regularly • • 37 who didn’t Reisfield, G. M., Bertholf, R., Barkin, R. L., Webb, F., & Wilson, G. (2006). Urine drug test interpretation: what do physicians know?. Journal of opioid management, 3(2), 80-86.
Reisfield, G. M., Bertholf, R., Barkin, R. L., Webb, F., & Wilson, G. (2006). Urine drug test interpretation: what do physicians know?. Journal of opioid management, 3(2), 80-86.
Reisfield, G. M., Bertholf, R., Barkin, R. L., Webb, F., & Wilson, G. (2006). Urine drug test interpretation: what do physicians know?. Journal of opioid management, 3(2), 80-86.
• 99 internal medicine residents • Compared personal confidence with interpreting drug screens vs. measured performance. Starrels, J. L., Fox, A. D., Kunins, H. V., & Cunningham, C. O. (2012). They don’t know what they don’t know: Internal medicine residents’ knowledge and confidence in urine drug test interpretation for patients with chronic pain. Journal of general internal medicine, 27(11), 1521-1527.
There was no significant differences in interpreting drug screens among medical residents stating confidence in their ability versus those acknowledging lack of confidence. Starrels, J. L., Fox, A. D., Kunins, H. V., & Cunningham, C. O. (2012). They don’t know what they don’t know: Internal medicine residents’ knowledge and confidence in urine drug test interpretation for patients with chronic pain. Journal of general internal medicine, 27(11), 1521-1527.
Brief History of Drug screening 1950’s blood 1950’s Emergency Rooms and Death “tox screens” investigations 1970’s: Addiction treatment & 1960’s TLC criminal justice 1970’s IA and 1970’s Methadone POC testing maintenance/Opioid Treatment/Military 1980’s IA + GC-MS Workplace/Industry/Govt. 21 st Century LC- Highway safety MS/MS
The Technology used for UDS
How are DOAs screened? Immunoassay GC-MS (Gas Chromatography coupled to Mass Spectrometry) LC-MS (Liquid Chromatography coupled to Mass Spectrometry)
Actually the following list is more accurate Method Common Abbreviation Cloned enzyme donor immunoassay CDIA Enzyme-linked immunosorbent assay ELISA Enzyme-multiplied immunoassay technique EMIT Fluorescence polarization immunoassay FPIA Radioimmunoassay RIA Point of care testing methods POCT Gas Chromatography Mass Spectrometry GC-MS Liquid Chromatography Ultraviolet Detection HPLC-UV Liquid Chromatography High Resolution Mass spectrometry LC-hrMS Liquid Chromatography tandem mass spectrometry LC-MS/MS Liquid Chromatography time-of-flight mass spectrometry LC-TOF Thin Layer Chromatography TLC
Immunoassay Urine Drug Screens (UDS) • Uses antibodies specific for drug or common metabolite target • Detection of a drug depends on antibody specificity, cut-off, and drug concentration. • Immunoassay-based Lab Methods • Automated on laboratory analyzers • Immunoassay-based POCT devices • Presence of band indicates a positive result
GC-MS Barbosa, S. S., Leal, F. D., Padilha, M. C., Silva, R. S., Pereira, H. M. G., Aquino Neto, F. R., & Silva Júnior, A. I. D. (2012). Specificity and selectivity improvement in doping analysis using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Química Nova, 35(5), 982-987.
LC-MS/MS 20 Eichhorst, J. C., Etter, M. L., Rousseaux, N., & Lehotay, D. C. (2009). Drugs of abuse testing by tandem mass spectrometry: a rapid, simple method to replace immunoassays. Clinical biochemistry, 42(15), 1531-1542.
UDS techniques are targeted or untargeted Targeted drug screens - identify specific drugs to screen excluding most others. • Most common: Immunoassay & LC-MS/MS • All UDS commonly used in NL are targeted. Untargeted drug screens – are broad drug screens without exclusion. • GC-MS and LC-hrMS methods are untargeted.
Comparison of UDS techniques Screening Screening/Confirmatory Analysis Immunoassay GC-MS or LC-MS/MS Ability to detect drug class Low to nil for synthetic opioids High (Sensitivity) but fair for others Ability to discriminate drug Variable-false positives and High from similar compounds false negatives (Specificity) Use Qualitative screen Quantitative confirmation Cost Variable Variable TAT rapid Many days Application Works best for screening drug- Definitive & Legally free population; may be less defensible useful in pain-management. Interpretation Complex Complex
Why urine?
Why is urine the most used sample? • Easy to obtain • Minimal preparation • Most drugs of interest & their metabolites concentrate in urine • Good sensitivity and specificity for recent use • Wider window of detection compared to blood
Positivity in urine indicates exposure ...But • Does not correlate with clinical status • Can miss very recent exposure • Positivity means different things depending on the screening method used.
Urine Drug Test Positive Negative Patient reports taking the drug True Positive False Negative 1. Patient is taking the drug as 1. Patient may be mistaken about reported. taking the drug. Yes 2. Test detects the substance 2. Last dose too low or too long ago to reported be detected. False Positive True Negative 1. Interfering substance 1. Patient is not taking the drug as 2. Unreported self- reported. No administration of a cross- 2. UDS does not detect the substance. reacting substance Interpreting urine drug screens
UDS Interpretation Factors Affecting UDS interpretation Amount of Time since ingestion Testing Method drug ingested Concurrent Individual Duration of use Diet Dosage Intervals Medications metabolism Administration Hydration Urinary Urine volume Urine pH Disease State Body Weight Route Status frequency
Interpreting UDS • Unexpected interferences • Target Compounds • Cut-offs • Windows of Detection • Importance of considering drug metabolism
Common Immunoassay Interferences Target Drugs Interfering Drugs Amphetamines Diet Pills, Vicks inhaler (US), Trazodone, Aripiprazole, Promethazine and Phentermine Marijuana Efavirenz (Antiretroviral), baby shampoo and soap, pantoprazole and possibly other proton pump inhibitors Hydromorphone Hydrocodone Methadone Quetiapine Fentanyl Trazodone TCAs Quetiapine Opiates/Morphine Poppy Seeds, Quinolone antibiotics Benzodiazepines Sertraline PCP Venlafaxine
Agents that can cause positive results on amphetamine immunoassay. Cross-reactivity is a common problem for UDS relying on immunoassay technique. Moeller, K. E., Lee, K. C., & Kissack, J. C. (2008, January). Urine drug screening: practical guide for clinicians. In Mayo Clinic Proceedings (Vol. 83, No. 1, pp. 66-76). Elsevier
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