33 Clinical Toxicology testing Flashcards
Why is urine preferred for tox screening?
- Concentration of drugs generally higher than in blood/ serum
- Easy to collect in sufficient volume
- Metabolite detection
- Screening assay compatibility
Limitations of Urine testing?
No relationship between detection and:
- actual ? time
- ? ingested
- ? of use/abuse
- Degree of ?
- Determining ? does not overcome these limitations
Difficult drugs:
eg Methylphenidate (?), oral ?
No relationship between detection and:
- actual ingestion time
- amount ingested
- frequency of use/abuse
- Degree of impairment
- Determining concentration does not overcome these limitations
Difficult drugs:
eg Methylphenidate (ritalin), oral hypoglycemics
General retention times in urine
see image
Testing methods and associated issues
Immunoassay - Initial testing
- ? reactions
- Refers to instrument bassed and non-instrument based techniques (?)
- Designed to detect a broad class of ?
- Limited in ?
- ? (the ability to detect a drug) dependent on reagent chemistry and devices used
- Prone to ? and ?
Main Advantage: 1
Main Disadvantage: 3
Immunoassay - Initial testing
- ? reactions
- Refers to instrument bassed and non-instrument based techniques (?)
- Designed to detect a broad class of ?
- Limited in ?
- ? (the ability to detect a drug) dependent on reagent chemistry and devices used
- Prone to ? and ?
Main Advantage: 1
Main Disadvantage: 3
Three reasons immunoassays might give false negatives?
- Cut offs are subjective (based on employment “rules”)
- Assay too specific (eg cocaine metabolite)
- Variance in antibody cross-reactivity within a drug class:
- Amphetamines
- Opiate: semi synthetics
- Benzodiazepine: glucuronid metabolites (lorazepam, temazepam)
Specimen integrity issues 4
Internal dilution
- Drinking lots of water
External Dilution
- Adding water to sample
Tampering
- adding an adulterant/masking agent to sample
Substitution
- donor submits a sample that is not their own
Non-clinical testing scenarios
Clinical toxicology testing is used for clinical management of patients
- Not for ? related purposes
- Not for ?
- Not for ?
- Not for ?
- Not for ?
Cannot be used as a measure of ?
Non-clinical testing scenarios
Clinical toxicology testing is used for clinical management of patients
- Not for employment related purposes
- Not for insurance
- Not for drug facilitated assault
- Not for accident investigation/impaired driving
- Not for Child apprehension of CPS
Cannot be used as a measure of impairment
STAT drug testing
* When? recommended
* A ? initiative
Qualitative toxicology testing is rarely of any value in
emergency situations for several reasons:
* It does not confirm or rule out ?.
* It almost never provides information that leads to a meaningful change in ?.
* Countless drugs contribute to ? seen in an emergency department that are not tested for by ?.
* The testing is ? (i.e. there are multiple false positives, which then require explanation and perhaps needless investigations).
* A positive test does not mean ?
- NOT recommended
- A provincial initiative
Qualitative toxicology testing is rarely of any value in
emergency situations 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 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.
What is Kinetic Interaction of Micro-particles in Sol’n (KIMS)
Principle:
Competitive ? ?
Components (2)
1. R1: ? derivatives conjugated to ?
2. R2: Micro-particles covalently coated with ?
What is Kinetic Interaction of Micro-particles in Sol’n (KIMS)
Principle:
Competitive Homogenous Immunoassay
Components (2)
1. R1: Drug derivatives conjugated to aminodextran
2. R2: Micro-particles covalently coated with antibody
Based on absorbance: Drug present = lower absorbance // no drug=higher abs.
KIMS Test Principle
When drug is present =
When drug is not present =
When drug is present = Low(er) absorbance
When drug is not present = High absorbance
Benzodiazepines (KIMS)
- Tends to be fairly ?
- Some ? more detectable than others
- Metabolite ? can be poor
- ? can cause a false positive
Benzodiazepines (KIMS)
- Tends to be fairly specific for benzos
- Some benzos more detectable than others
- Metabolite cross reactivity can be poor
- Oxaprozin (Daypro) can cause a false positive
Confirmatory Testing
- Main advantage?
- Main Disadvantage?
Confirmatory Testing
- Main advantage?
- Definitive
- Main Disadvantage?
- More resource driven compared to immunoassay
What is GC/MS analysis
Gas chromatography–mass spectrometry (GC-MS) is an analytical method that combines the features of gas-chromatography and mass spectrometry to identify different substances within a test sample
- Marijuana metabolite (SIM)
- Cocaine metabolite (SIM)
SIM = Selective ion monitoring
GC/MS or LC/MS/MS testing
- More ? than the immunoassay
- Gives a fingerprint of drug based on ? and ?
- Identify ? compounds
- Considered ? tests
- Poor ? and/or poor ? properties of some drugs limits detection
GC/MS or LC/MS/MS testing
- More resource driven than the immunoassay
- Gives a fingerprint of drug based on retention time and fragmentation pattern
- Identify specific compounds
- Considered confirmation tests
- Poor extraction and/or poor chromatographic properties of some drugs limits detection
What is LC/MS/MS?
What drugs does it identify?
Liquid Chromatography with tandem mass spectrometry (LC-MS-MS)
analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry
Opioid identification
