What Does the Drug Test Tell Us QUALITATIVE TOXICOLOGY TESTING for CLINICAL MANAGEMENT of the PATIENT Background • The qualitative drug test is often referred to as the “drug screen” - a misnomer • Testing performed using: – Immunoassay – GC/MS or LC/MS/MS confirmation techniques 2 1 Immunoassay – Initial Testing • Antigen-Antibody reactions • Refers to instrument based and non-instrument based techniques • Designed to detect a broad class of drugs • Cross-reactivity (the ability to detect a drug) dependent on reagent chemistry and devices used • Limited in scope (i.e. limited number of assays available) • Prone to false negatives and false positives 3 Confirmation Testing • Uses GC/MS or LC/MS/MS techniques • Confirms immunoassay result or initial testing for drugs in which no immunoassay available. • More resource driven than immunoassay • Provides specificity that cannot be achieved with immunoassay 4 2 Amphetamines (CEDIA) • Designed to detect methamphetamine, amphetamine and MDMA (same or different assays) • Will potentially detect other amphetamine like drugs PMMA/PMA pseudoephedrine/ephedrine phentermine phenylpropanolamine mephentermine • Will detect non-amphetamine like drugs bupropion trifluoromethylphenylpiperazine (TFMPP) trazodone m-CPP (trazadone metabolite/BZP analog) ranitidine phenelzine breakdown fenofibrate 5 Cocaine Metabolite (KIMS) • Tends to be specific for cocaine metabolite (benzoylecgonine) • Cocaine can be used in hospital type procedures – Eye surgery – Nasal surgery • Cutting Agents – levamisole, diltiazem, hydroxyzine, phenacetin, benzocaine 6 3 Cocaine Cut in Alberta* 40.0% 34.8% 35.0% 33.3% 28.4% 30.0% 27.4% 24.1% Levamisole 25.0% Benzocaine 20.0% 15.5% Phenacetin 15.0% 9.8% Diltiazem 10.0% 6.9% 5.0% 3.0% 851 819 90 966 448 201934 262 646 0.0% Apr/09 ‐ Mar/10 Apr/10 ‐ Mar/11 Apr/11 ‐ Mar/12 *Data Courtesy Controlled Substances and Tobacco Directorate, Health Canada 7 Cocaine Pharmaceutical Cutting Agents UAH Percent of Cocaine Confirmed Specimens Containing Cutting Agents 80.0% 69.5% 70.0% 63.0% 60.0% 58.6% 50.0% 2010 40.0% 2011 2012 30.0% 25.0% 20.0% 18.3% 10.0% 4.0% 5.0% 1.5% 1.4% 0.0% Levamisole Phenacetin Diltiazem 8 4 Opiates (KIMS) • Designed to pick up morphine and codeine • Will detect other opioids but not as well – hydrocodone – hydromorphone • Does not detect: – methadone/methadone metabolite (specific immunoassay) – buprenorphine (detected using LC/MS/MS) • Detects oxycodone poorly (specific immunoassay) • Ofloxacin and rifampin can cause a false positive 9 Benzodiazepines (KIMS) • Tends to be fairly specific for benzodiazepines • Some benzodiazepines more detectable than others • Metabolite cross-reactivity can be poor • Oxaprozin (Daypro) can cause a false positive • Cross-reactivity table 10 5 Generic Name Trade Name 300 ng/mL Equivalent % Cross-Reactivity Clobazam 382 79 Chlordiazepoxide Librium 486 62 Desmethylchlordiazepoxide 517 58 Clonazepam Klonopin 445 67 7-aminoclonazepam 489 61 Flunitrazepam Rohypnol 424 71 7-aminoflunitrazepam 333 90 desmethylflunitrazepam 395 76 3-hydroxyflunitrazepam 584 51 Flurazepam Dalmane 490 61 Hydroxyethylflurazepam 347 87 didesethylflurazepam 423 71 Desalkylflurazepam 323 93 Lorazepam Ativan 487 62 Lorazepam glucuronide >20,000 1.1 Midazolam Versed 467 64 -hydroxymidazolam 431 70 Temazepam Restoril 409 73 Temazepam Glucuronide >20.000 1.0 Triazolam Halcion 352 85 -hydroxytriazolam 377 80 4-hydroxytriazolam 385 78 11 Marijuana Metabolite • Designed to detect the marijuana metabolite - 11-nor- 9-tetrahydrocannabinol-9-carboxylic acid but will detect other metabolites • Historically assay was quite robust • New techniques saw emergence of false positives: – pantoprazole / Pantoloc (for acid-reflux) and POCT devices – efavirenz / Sustiva (anti-viral) and CEDIA chemistry • Passive exposure • Baby wash products vs metabolites normally occurring in neonates 12 6 GC/MS or LC/MS/MS Confirmation Testing RECEIVE URINE • More resource driven than the immunoassay SAMPLE PREPARATION - EXTRACTION GC/MS (2 mL to 10 uL) • Gives a fingerprint of drug LC/MS/MS (1 mL to 250 uL) based on retention time and fragmentation pattern INJECTION ON GC/MS or LC/MS/MS • Identify specific compounds SEPARATION in GC or LC (Retention Time) • Considered confirmation tests FRAGMENTATION in MS (Library Match/SIM or MRM) 13 General Retention Times • Amphetamines up to 4 days • MDMA (Ecstasy) up to 4 days • Marijuana Metabolite up to 30 days (chronic vs occasional) • Cocaine metabolite up to 4 days • Opiates up to 3 days • Heroin Metabolite less than 1 day • Barbiturates days to weeks • Benzodiazepines days to weeks • Methadone up to 3 days • Alcohol less than 1 day 14 7 The STAT Drug Test • Qualitative toxicology testing is rarely of any value in emergent situations for the acute management of patients for several reasons: – It does not confirm or rule out significant poisoning. – It almost never provides information that leads to a meaningful change in acute medical management. – Countless drugs contribute to common clinical symptoms seen in an emergency department that are not tested for/detectable by immunoassay screening tests. – The testing is not specific (i.e. there are multiple false positives, which then require explanation and perhaps needless investigations). – A positive test does not mean that this is what is contributing to the patient's symptoms. • NOT diagnostic – cannot be used to diagnose poisoning 15 Qualitative Urine Drug Testing - AHS • Cannot be used as a measure of impairment • Not for employment related purposes • Not for insurance purposes • Not for drug facilitated assault • Not for accident investigation/impaired driving • Not for apprehending children under child and family services authorities • Use for the CLINICAL management of patients – determining compliance challenging 16 8 Contact Information - Toxicologists • Dr. Penny Colbourne 780-407-4729 • Dr. Don LeGatt 780-407-8444 • For acute management of the poisoned patient contact PADIS 1-800-332-1414 17 9.