Transcript monitoring compliance with treatment

Urine Drug Testing
Comparisons Of Different
Modalities
Michael Casarico LADC
Creating Opportunity To Embrace Recovery
LESS
CRAVING
NEEDED
THERAPIES
MAT
STABILITY
NO
WITHDRAWAL
Abstinence Reinforcements
Drug Free Test Result
Affirmation of progress
Increase in motivation
Empowerment
Restoration of privilege
Self esteem
Deepening commitment
Strengthening of recovery
Presence Of Drug Detected
Adjustment of treatment plan
Increase in motivation
Possible suspension of privilege
Abstinence Reinforcements
• Random Urine Collection
Prevents Opportunities For Tampering
• Observed Urine Collection
Creates High Degree Of Specimen Integrity
Point of Care Testing (POCT)
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One examination of LC-MS/MS results following immunoassay POC testing in
addiction treatment settings found high rates of clinically false negatives, that
is, samples tested by POC were reported negative but LC-MS/MS results were
positive. Twenty-nine percent of opioids other than methadone identified by
LC-MS/MS were missed by POC tests; 28% methadone, 43% amphetamines,
35% benzodiazepines, 40% cocaine and 20% marijuana. Additionally,
investigators found rates of office-based false positive results including 22% of
opioids other than methadone identified as positive on POC but negative on
LC-MS/MS, 46% methadone, 21% amphetamines, 61% benzodiazepines, 12%
cocaine and 21% marijuana.
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How POCT Works
Antibody
Antigen
Drug
Negative Sample
Positive Sample
How POCT Works
• That reaction (color change, fluourescence, chemiluminescence,
etc) can then be “read” by an internal detector in the screening cup
to yield a result.
• Take home message: negative samples typically have more of a
reaction occurring than positive samples.
Confirmation Testing
Testing in a Lab
Advantages
•
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•
•
•
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Higher Precision
Laboratory Professionals
Drug Quantitation
Specific Drug Used
Confirmation on Sample
Trained Professionals
Disadvantages
• Turn Around Time
Why Use Urine?
• Urine is by definition concentrated
• Urine shows recent exposure.
• Is an easy and non-invasive collection (does require same
gender collector for observed collections)
• Is a relatively safe biological product to handle.
• Both drugs and their metabolites can be seen in many cases
– extends out the detection window. (blood and Oral Fluids
show current use)
• Drugs/metabolites often present in higher concentrations
than blood or oral fluid (easier to detect)
• Sample tracked from start to finish. Minimum of TWO
identifiers (must match between the cup and the identifiers on
requisition). Minimizes/reduces the chance of sample mix ups.
• Two stages of Testing: (1) Screening (2) Confirmation
• Screening:
• Performed using Immunoassay. Relatively quick.
• Sensitive but not always specific. (Identify class vs. specific
analyte)
• Prone to cross-reactivity.
• Confirmation:
• Performed using LC-MS/MS and GC-MS/MS.
• Sensitive and Specific. Identifies each drug with certainty.
• Checks performed at every step of setup & identification to
ensure highest quality of sample.
• Confirmation testing requires time.
Immunoassay Drug Screening
• Specialized test that exploits antibody/antigen relationships
• Antibodies are a type of protein produced by the immune
system in response to foreign substances antigens
(unexpected substances). Think of the antibodies as the
“warriors” sent out to neutralize the antigens, the “invaders”
• Antibodies bind to the antigen responsible for their production
Screening
Qualitative Results: positive or negative
• Is the drug concentration above the cut-off level: yes/no
Cut-off Levels: The cut-off for a test gives a defined drug concentration,
typically measured using ng/ml.
• Example: cut-off for Opiates is 300 ng/ml
• Most labs use the SAMSHA guidelines for cut-off levels
Analyzer: Utilizes EIA (Enzyme Immunoassay) technology
Rapid Turn Around Time: 24 Hours
Window of Detection/Test Scheduling
SAMHSA
Examples of potential false
positives due to crossreacting compounds for
certain immunoassays
UDT 6 p15
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EIA – Enzyme Immunoassay
• All “liquid”
• Automated
• Somewhat specific
• Some assays look for specific drugs
• Some assays look for drugs within a certain class
• Rapid
• Uses large, high sample capacity analyzers
• Ability to give a semi-quantitative result
Validities
Use at least four “validity” parameters: pH, General Oxidants,
Specific Gravity and Creatinine. These tests are performed to test
for ADULTERANTS.
• If any of these are outside normal parameters, the sample is
flagged.
• These values can help pinpoint if a sample has been
adulterated or tampered with.
• Acceptable ranges are listed on every report.
Validities (cont’d)
pH = measurement of how acidic or basic the specimen
is, if below 3 or above 11, sample is rejected as unsuitable
for EIA testing.
General Oxidants – one way of adulterating samples is to
add an oxidizing substance into it to break down the
offending drug rendering it undetectable.
Specific Gravity – measures the “urine density”; the
concentration of all chemical entities within the urine. A
good marker for water balance and kidney function.
Validities (cont’d)
Creatinine - Breakdown product of creatine phosphate in
the muscle, a product of a normal biological function
<20 = “dilute” or overhydrated
>400 = very concentrated
Some agencies call any sample with a Specific Gravity
lower than cutoff and a creatinine <20 “dilute,” and
therefore considered positive.
In assessing unusual or suspect results, Creatinine and
Specific Gravity are closely evaluated.
C.O.P.S.
Creatinine
Oxidants (General)
pH
Specific Gravity
Drug Screening Summary
• Drug Screening can be used for many purposes.
• Results can indicate that a sample may require closer scrutiny.
• Screening is not always specific enough to give detail on
exactly what drug is in a person’s system – may just be a drug
class – and not all drugs are offered as a screen.
• While “generally accurate” there can be other substances that
cross react and “trick” the screen into being positive.
• To find out for certain what drug and what amount is in a
sample, a “confirmatory” or “definitive” test must be performed.
Specialized extraction and analysis is performed on the
selected sample.
Confirmations
• The term “drug confirmation” comes from the law enforcement
arm of forensic toxicology. “Confirming the presence of an
offending substance”
• For something to be considered a true confirmation, it must be
a second aliquot of the sample and must be determined by an
alternative technology.
• Screening is performed by EIA – enzyme immunoassay.
The portion of the urine specimen used for that is discarded.
Another portion is removed from the specimen cup and
analyzed by a chromatographic and mass spectrometric
(mass spec) technique.
Semantics
• Confirmation is vernacular for testing and identifying the presence
of a specific drug.
• Also known as Directed Analysis and Targeted Analysis.
• A quantitative confirmation will give you a specific amount of drug
in the urine and the exact drug found
• A qualitative confirmation will tell you that a drug in is present.
• Screening often tells you if a drug class, not a specific compound,
is present.
How it works…
“Confirm all positives”
• Sample is received, accessioned and screened.
• Screening data is “accepted” into the LIMS system and that triggers the order in the
LIMS system for confirmations.
• The confirm ordered samples are retrieved and a portion of it is placed into a test tube.
• That sample then undergoes a series of sample preparation steps before being placed
onto the LCMSMS or GCMS.
• The instrument identifies the exact drug by its “retention time” – how long it takes to
separate from everything else in the sample and it’s mass spectral identification
(chemical fingerprint)
• The amount of the drug is determined by the size of the peak displayed.
Why Perform Confirmation Testing?
• Screening may only detect someone is positive for a class of drugs – may
not be able to pinpoint the exact drug.
• Screening cutoffs are typically higher than confirm cutoffs.
• Screening at best gives a “semi-quantitative” result – a ballpark.
• Screening does not “see” all metabolites. Could miss cases of diversion.
• Screening kits aren’t always sensitive to all drugs in the class, some drugs
no screen exists.
• ANYTIME there’s possibility of legal action, a confirmation should be
performed.
Substance Use Testing for Buprenorphine
• Reliable Screening Results – Cutoff is 20 nanograms (ng) per
milliliter (ml)
• Very low rate of False Positive Reports
• Confirmation by LCMS/MS - LOQ is 5 ng/ml for both Buprenorphine
and its metabolite Norbuprenorphine
Substance Use Testing Complications
• Screening does not necessarily test for Buprenorphine and its
metabolite, Norbuprenorphine.
• It is possible for a donor to add a trace of their medication to their
urine sample (“spike”), thus causing a positive screen while not
having actually taken the medication.
• An LCMS/MS Confirmation of this same sample will report that the
metabolite, Norbuprenorphine, is not present at an appropriate
level, therefore the sample tested positive on the Screen because of
the Parent Drug itself being present in the sample.
Importance of reliable
testing as a means of
motivating a client
Substance Use Testing for Other Opioids
Further Testing Report Examples
Report
Report
Questions ~ Comments
Thank You For Your Time And Attention
References
• White Paper ASAM
http://www.asam.org/docs/default-source/public-policystatements/drug-testing-a-white-paper-by-asam.pdf?sfvrsn=2
• Clinical Drug Testing In Primary Care SAMHSA
http://store.samhsa.gov/product/TAP-32-Clinical-Drug-Testing-inPrimary-Care/SMA12-4668
• Urine Drug Testing In Clinical Practice: The Art And Science Of
Patient Care Edition 6 Center for Independent Health Care
Education