What Does the Drug Test Tell Us

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Isabel Garrison
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1 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

test is often referred to as the drug screen - a misnomer Testing

2 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

3 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

trifluoromethylphenylpiperazine (TFMPP) m-cpp (trazadone metabolite/bzp analog) phenelzine breakdown 5 Cocaine Metabolite (KIMS) Tends to be specific for cocaine

4 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% 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% % 18.3% 10.0% 0.0% 4.0% 5.0% 1.5% 1.4% Levamisole Phenacetin Diltiazem 8 4

Controlled Substances and Tobacco Directorate, Health Canada 7 Cocaine Pharmaceutical Cutting Agents UAH 80.0% 70.0% 60.

5 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

Ofloxacin and rifampin can cause a false positive 9 Benzodiazepines (KIMS) Tends to be fairly specific for benzodiazepines Some

6 Generic Name Trade Name 300 ng/ml Equivalent % Cross-Reactivity Clobazam Chlordiazepoxide Librium Desmethylchlordiazepoxide Clonazepam Klonopin aminoclonazepam Flunitrazepam Rohypnol aminoflunitrazepam desmethylflunitrazepam hydroxyflunitrazepam Flurazepam Dalmane Hydroxyethylflurazepam didesethylflurazepam Desalkylflurazepam Lorazepam Ativan Lorazepam glucuronide >20, Midazolam Versed hydroxymidazolam Temazepam Restoril Temazepam Glucuronide > Triazolam Halcion hydroxytriazolam hydroxytriazolam 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

71 Desalkylflurazepam 323 93 Lorazepam Ativan 487 62 Lorazepam glucuronide >20,000 1.

7 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

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

8 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

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).

9 Contact Information - Toxicologists Dr. Penny Colbourne Dr. Don LeGatt For acute management of the poisoned patient contact PADIS

DUI in Southern Ohio MATT 2006

DUI in Southern Ohio MATT 2006 Laureen J. Marinetti, M.S., Ph.D. Chief Toxicologist Montgomery County Coroner s s Office & Miami Valley Regional Crime Lab (MVRCL) Dayton, Ohio Region The MVRCL is a regional