QUALITATIVE TOXICOLOGY TESTING for
CLINICAL MANAGEMENT of the
PATIENT
What Does the Drug Test Tell Us
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Background
• The qualitative drug test is often referred to as the “drug screen” - a misnomer
• Testing performed using: – Immunoassay
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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
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
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Amphetamines (CEDIA)
• Designed to detect methamphetamine, amphetamine and MDMA (same or different assays)
• Will potentially detect other amphetamine like drugs
• Will detect non-amphetamine like drugs
PMMA/PMA pseudoephedrine/ephedrine
phentermine phenylpropanolamine
mephentermine
bupropion trifluoromethylphenylpiperazine (TFMPP)
trazodone m-CPP (trazadone metabolite/BZP analog)
ranitidine phenelzine breakdown
fenofibrate
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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
7 28.4% 33.3% 34.8% 15.5% 9.8% 6.9% 24.1% 3.0% 27.4% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0%
Apr/09 ‐ Mar/10 Apr/10 ‐ Mar/11 Apr/11 ‐ Mar/12
Levamisole Benzocaine Phenacetin Diltiazem 934 966 851
*Data Courtesy Controlled Substances and Tobacco Directorate, Health Canada
819 90 448 201 262 646
Cocaine Cut in Alberta*
Cocaine Pharmaceutical Cutting Agents UAH
63.0% 4.0% 5.0% 69.5% 18.3% 58.6% 25.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0%
Percent of Cocaine Confirmed Specimens Containing Cutting Agents
2010 2011 2012
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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
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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
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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
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
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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)
FRAGMENTATION in MS (Library Match/SIM or MRM)
• More resource driven than the immunoassay
• Gives a fingerprint of drug based on retention time and fragmentation pattern
• Identify specific compounds • Considered confirmation tests
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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
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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
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 CLINICALmanagement of patients – determining compliance challenging
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