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 phentermine mephentermine pseudoephedrine/ephedrine phenylpropanolamine Will detect non-amphetamine like drugs bupropion trazodone ranitidine fenofibrate trifluoromethylphenylpiperazine (TFMPP) m-cpp (trazadone metabolite/bzp analog) phenelzine breakdown 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% 35.0% 30.0% 25.0% 20.0% 15.0% 10.0% 5.0% 0.0% 33.3% 34.8% 28.4% 27.4% 24.1% 15.5% 9.8% 6.9% 3.0% 851 819 90 966 448 201 934 262 646 Apr/09 Mar/10 Apr/10 Mar/11 Apr/11 Mar/12 Levamisole Benzocaine Phenacetin Diltiazem *Data Courtesy Controlled Substances and Tobacco Directorate, Health Canada 7 Cocaine Pharmaceutical Cutting Agents UAH 80.0% 70.0% 60.0% Percent of Cocaine Confirmed Specimens Containing Cutting Agents 69.5% 63.0% 58.6% 50.0% 40.0% 30.0% 25.0% 2010 2011 2012 20.0% 18.3% 10.0% 0.0% 4.0% 5.0% 1.5% 1.4% 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 SAMPLE PREPARATION - EXTRACTION GC/MS (2 ml to 10 ul) LC/MS/MS (1 ml to 250 ul) INJECTION ON GC/MS or LC/MS/MS SEPARATION in GC or LC (Retention Time) More resource driven than the immunoassay Gives a fingerprint of drug based on retention time and fragmentation pattern Identify specific compounds 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