Download Drug Testing 2016 - Governor`s Institute on Substance Abuse

Drug Testing 2016
J. Paul Martin, MD, DFASAM
Medical Review Officer
&
Outline
• History and use of drug testing in the clinical
setting
• Who, what, when, where, how, and why
• Behind the curtain – testing
• What’s in this urine?
• Your conundrums: audience submits cases
Employment
Testing
Therapeutic
Testing
History of Drug Testing in the US
• Employment Testing
–Federally Regulated
Employees
–Non-Federally Regulated
Employees
• Therapeutic Testing
Why Test?
• The primary purpose of the Federal
workplace-based drug testing program is
to deter use of illegal substance of abuse
in large groups of individuals subject to
testing, and detect those individuals
clearly using illicit drugs.
Why Test?
Safer Workplace
• Applied to Federal facilities (except
Congress) but adopted by others largely
to gain workman’s compensation
insurance benefits.
History of Drug Testing in the US
• Executive Order
12564 Sept. 1986
established the
Federal Drug-Free
Workplace
Program
History of Drug Testing in the US
• October 1991 –
• The Hollings/Danforth bill passes
as the Omnibus Transportation
Employee Testing Act of 1991
• Mandatory testing of all
“safety sensitive”
History of Drug Testing in the US
• October 1991 –
• The Hollings/Danforth bill passes
as the Omnibus Transportation
Employee Testing Act of 1991
• Mandatory testing of all
“safety sensitive”
History of Drug Testing in the US
• FAA
• FMCSA
• FRA
• FTA
• MARAD (Coast Guard)
• PHMSA (pipeline)
 12 Million Individuals
History of Drug Testing
• 1994 DOT testing expanded to include all
commercial drivers
• 1995 Alcohol testing for large Companies
• 1996 Alcohol testing for all
• 2001 DOT revision addressing validity
testing and training
Complaints of Governmental Oppression
• “Right to Privacy”
• Politics mandated initial testing for “illicit
drugs” to include marijuana, cocaine,
PCP, amphetamines,
heroin/morphine/codeine
• Did not initially include
alcohol.
Shortfall of the DOT & Federal Testing Programs
Other than THC and Cocaine, the “NIDA 5”
missed the commonly abused drugs
Shortfall of the DOT & Federal Testing Programs
Pending Proposals to Expand Federally
Mandated Testing to Include:
1. Saliva Testing
2. Include Hydrocodone &
Oxycodone, Oxymorphone &
Hydromorphone
History of Drug Testing in the US
• Employment Testing
Federally regulated
employees
– Non-Federally Regulated
Employees
• Therapeutic Testing
Private Drug Testing in US
• Private employers do not have to worry
about “right to privacy” as long as policies
are nondiscriminatory.
• In addition to THC/cocaine,
benzodiazepines, synthetic narcotics,
barbiturates, anabolic steroids, club drugs,
etc. can be screened
Quest Labs
Quest Labs
Private Drug Testing in US
• At Will Employment – NC GS 41-1-110
Private Drug Testing in US
• At Will Employment – NC GS 41-1-110
NC Department of Labor
• North Carolina General Statutes
Chapter 95, Article 20
AND
• North Carolina Administrative Code
Title 13, Chapter 20
NC Department of Labor
• Point of Care single use device may be
used for prospective employees
• Existing employees must be tested by an
authorized laboratory
Complaints of Oppression from the Man
Attempts to foil toxicology testing
•
•
•
•
Dilution
Detoxification
Adulterants
Substituted Specimen
Dilution
INITIAL TEST CUTOFF LEVELS FOR DRUGS AND
DRUG METABOLITES FMCSA
Drug or metabolites
Marijuana metabolites
Cocaine metabolites
Opiate metabolites
Phencyclidine (PCP)
Amphetamines
(Dilution is the solution to pollution)
Cutoff level
[nanograms (ng)/mL]
50
150
2000
25
500
Attempts to foil toxicology testing
Dilution
• Detoxification
• Adulterants
• Substituted Specimen
Directions for Use
Drink 32oz. of water one hour before drinking product.
32 OZ
Shake well and drink entire bottle.
16 OZ
Refill product bottle with water right away and drink at a moderate pace. 16 OZ
Urinate as often as possible to expel toxins.
Urinate at least three to four times after drinking product. The more the better.
Product is effective in 45 minutes and up to three hours. However, product is
most effective between 1 to 2 hours after consumption.
Directions for Use
Drink 32oz. of water one hour before drinking product.
32 OZ
Shake well and drink entire bottle.
16 OZ
Refill product bottle with water right away and drink at a moderate pace. 16 OZ
Urinate as often as possible to expel toxins.
Urinate at least three to four times after drinking product. The more the better.
Product is effective in 45 minutes and up to three hours. However, product is
most effective between 1 to 2 hours after consumption.
Attempts to foil toxicology testing
Dilution
Detoxification
• Adulterants
• Substituted Specimen
NuKlear (URINE ADDITIVE) was perfected
after thousands of hours of lab work. It is a
great breakthrough - the smallest, most
potent, undetectable urine purifier sold
today. It's predecessor "Klear" was so
successful that the drug testing industry
devised a test specifically to test for
"Klear." Counter measures were called for
and after a year and a half your scientists
perfected "NuKlear." "NuKlear" CLEARS
ALL POSITIVES. For large samples of
more than 4oz. use two tubes. If kept
sealed in it's tube, "NuKlear" remains
potent for up to two years.
Occupy Urine Tests!
Worker Rights Special: Buy 1 get 1 free
$34.95 + S&H
Validity Testing
•
•
•
•
•
Specific Gravity >1.001 and <1.030
Creatinine >2 mg/dl
Temperature 90° - 100°
pH > 4.5 < 9 normal range
pH absolute invalid <3 >11
Attempts to foil toxicology testing
Dilution
Detoxification
Adulterants
• Substituted Specimen
Attempts to Substitute
Whizzinator - $99.95
*available in several skin tones including fleshtone,
tan, brown, dark brown, black and pink
Attempts to foil toxicology testing
NC GS 14-401.20 (2003)
• The sale of urine or adulterants or attempt to
foil a drug test is punishable as a Class 1
misdemeanor: 1-45 days community svc.
• A second offense is punishable as a Class I
felony: 4 – 6 months prison
Attempts to foil toxicology testing
SC Code Ann 16-13-470 (2003)
• The sale of urine or adulterants or attempt to
foil a drug test is punishable as a misdemeanor
– not more than $5K &/or up to 3 yrs
• A second offense is punishable as a Class I
felony – not more than $10K &/or up to 5 yrs
Attempts to foil toxicology testing
Dilution
Detoxification
Adulterants
Substituted Specimen
History of Drug Testing in the US
• Employment Testing
Federally Regulated
Employees
Non-Federally Regulated
Employees
• Therapeutic Testing
Employment
Testing
Therapeutic
Testing
Employment
Testing
Therapeutic
Testing
Office Based Drug Screening
• Why are we drug screening?
• Tests available today
• Differences between Point-of-Care Screening
& Confirmation Testing in certified labs
• How many panels do you really need?
• Importance of understanding metabolites
• Practical & tactical considerations
Why are we screening?
• To Protect the Patient
• To Protect the Public
• To Protect the Physician
Who are we screening?
• Those on Controlled Substances
opiates
benzodiazepines
amphetamines
• Recovery Monitoring
Special screening situations?
• Emergency Rooms – altered Mental
Status, MVA, work related injuries
• Transplant programs
• May need confirmation!
Standards of Care
Standards of Care
June 2014
Standards of Care
Monitoring Individuals on CS
• Patient – pain relief, quality of life, stressors,
adherence to plan, aberrant behaviors,
physical exam
• Family monitor
• Controlled Substance Reporting System
• Pill counts
• Discussion with therapist
• Periodic drug screening
Tests available today
•
•
•
•
•
Saliva
Hair
Sweat
Blood
Urine
Saliva Testing
$5.85 ea.
Coc/mAmp/Amp/Opi/THC/PCP
$7.85
Tests available today
Saliva
• Hair
• Sweat
• Blood
• Urine
How Much Hair for Test?
How Much Hair for Test?
How Much Hair for Test?
Walmart $63
Tests available today
Saliva
Hair
• Sweat
• Blood
• Urine
Drug Detection Periods in Different Specimen Sources
(Adapted from E.J. Cone, Addiction Research Center)
Drugs and their metabolites are found throughout the body after use
Standard office drug test collection:
Screening vs Confirmation
SCREENING
• The test is performed to detect the presence of
specific drugs/metabolites or classes in the urine
• The test indicates recent use of the drug
• The test is presumptive of the drug’s presence but
not to a level of forensic confidence
• The test may need to be confirmed to a higher level
of certainty
Importance of Cutoff Levels
INITIAL TEST CUTOFF LEVELS FOR DRUGS AND
DRUG METABOLITES
Drug or metabolites
Marijuana metabolites
Cocaine metabolites
Opiate metabolites
Phencyclidine (PCP)
Amphetamines
Cutoff level
[nanograms (ng)/mL]
50
150
2000
25
500
SCREENING
• Immunoassays – 5 types
– Antibody based tests
• Designed to target a specific chemical
– Parent drug or metabolite
• Selected to give “good window of detection”
• Specificity of antibodies varies
– Some assays are specific for a given drug
– Others designed to detect classes of drugs
• Sensitivity (cut-off)
– Threshold or level defining a “positive” versus a “negative”
result
– Determined by manufacturer (occasionally lab)
CLIA Waived
Enzyme/Antibody Poisons
•
•
•
•
•
•
•
Tetrahydrozoline (eye drops)
Bleach
Vinegar
Soap
Ammonia
Lemon juice
Drain cleaner
• Table salt
• Various chemicals
(glutaraldehyde, sodium or
potassium nitrate,
pyridinium chlorochromate,
and peroxide/peroxidase)
CONFIRMATION
• Second analytical procedure with higher
specificity (list of compounds detected or
identified narrowed)
– Gas chromatography/mass spectrometry (GC/MS)
– Liquid chromatography/tandem mass spectrometry
(LCMSMS, HPLCMS)
• And with better sensitivity
– Cut-offs are lower
– but still NOT 0!
How Many Panels?
One Panel
Fifteen Panels
How Many Panels?
•
•
•
•
•
•
•
•
•
Drug being prescribed
Marijuana / Cocaine
Oxycodone
Buprenorphine
Methadone
Opiates (Morphine, codeine, hydrocodone)
Alprazolam (Xanax) / clonazepam (Klonopin)
Amphetamines
Others based on local drug use/availability
Office Based Drug Screening
Why are we drug screening?
Tests available today
Differences between Point-of-Care Screening
& Confirmation Testing in certified labs
How many panels do you really need?
• Importance of understanding metabolites
• Practical & tactical considerations
Opiate Metabolism
<11%
<2.5%
Benzodiazepine Metabolism
Office Based Drug Screening
Why are we drug screening?
Tests available today
Differences between Point-of-Care Screening
& Confirmation Testing in certified labs
How many panels do you really need?
Importance of understanding metabolites
• Practical & tactical considerations
Drug Testing Case Studies
• Your recovering addict on hydrocodone for a
broken ankle screens positive for THC
• She reassures you, “Doc there’s no way I’d
abuse Marijuana, knowing that you’d test me.
I was at a party last weekend and it was really
smoky in the room.”
• Is passive exposure a reasonable explanation?
Importance of Cutoff Levels
INITIAL TEST CUTOFF LEVELS FOR DRUGS AND
DRUG METABOLITES
Drug or metabolites
Marijuana metabolites
Cocaine metabolites
Opiate metabolites
Phencyclidine (PCP)
Amphetamines
Cutoff level
[nanograms (ng)/mL]
50
150
2000
25
500
Practical & Tactical Issues
Passive exposure
• How often to drug screen?
• Controverted results
• Cost considerations
• Positive result mandates change of care plan
• Referral for S.U.D. evaluation/treatment
• Most important part of monitoring program is
the physician-patient relationship
How often is reasonable
• Most drugs are present in the urine for less
than 3 days.
• For a recovery program that required
inpatient treatment: twice weekly for a year.
• Intermittently run a random test.
How often to test?
• For high risk medication, collect a specimen at
each visit…actually run a test periodically.
• Be sure to test for common opiates of abuse,
and make sure your benzodiazepine test
includes alprazolam and clonazepam.
 Test for the high risk med you prescribed
How often to test?
• A diagnosis of drug abuse should not be made
on the urine drug level
• There is no scientifically validated relationship
between the amount of the drug taken and
the urine drug test concentration.
Controverted test?
• Punt for confirmation
Practical & Tactical Issues
Passive exposure
How often to drug screen?
Controverted results
• Cost considerations
• Positive result mandates change of care plan
• Referral for S.U.D. evaluation/treatment
• Most important part of monitoring program is
the physician-patient relationship
Recent Billed Charges
• $1,480.30 Millennium Labs
• $3,607.93 Oaktree Medical Centre
• $1,130 Physician Choice Laboratory
• Dx – long-term (current) use of other
medications, encounter for therapeutic drug
monitoring.
Medicaid / Medicare
Reimbursement
• Medicaid: 80300
• Medicare: G0477
• $14.88
Practical & Tactical Issues
Passive exposure
How often to drug screen?
Controverted results
Cost considerations
• Positive result mandates change of care plan
• Referral for S.U.D. evaluation/treatment
• Most important part of monitoring program is
the physician-patient relationship
Therapeutic drug testing
• What did you expect the test to show?
• A positive test requires a change in
treatment plan
• Don’t abandon the patient because of an
abnormal drug test
Therapeutic drug testing
• What did you expect the test to show?
• A positive test requires a change
in treatment plan
• Don’t abandon the patient because of an
abnormal drug test
Therapeutic drug testing
• What did you expect the test to show?
• A positive test requires a change in
treatment plan
• Don’t abandon the patient because of an
abnormal drug test
Practical & Tactical Issues
Passive exposure
How often to drug screen?
Controverted results
Cost considerations
Positive result mandates change of care plan
• Referral for S.U.D. evaluation/treatment
• Most important part of monitoring program is
the physician-patient relationship
Why are we screening?
• To Protect the Patient
• To Protect the Public
• To Protect the Physician
Office Based Drug Screening
Why are we drug screening?
Tests available today
Differences between Point-of-Care Screening
& Confirmation Testing in certified labs
How many panels do you really need?
Importance of understanding metabolites
Practical & tactical considerations
Outline
History and use of drug testing in the clinical
setting
Who, what, when, where, how, and why
• Behind the curtain – testing
• What’s in this urine?
• Your conundrums: audience submits cases
How: or, Behind the Curtain….
• A peek into laboratory
testing
Collection is Key!
• No coats, purses, etc in
bathroom
• Turn off water at sink
• Use colored (blue, green)
disinfectants in toilets
• Use collection containers
with temperature indicators
(AND READ THEM)
• Observed collection
– NOT foolproof
• FOLLOW PROTOCOLS for hair
and oral fluid

NEVER, NEVER EVER encourage fluid
intake!!!!!!!!!!!!!!!!!!!!
Moving from Collection
To Testing….
SCREENING
Report
Toxicology
Urine toxicology
screen
Opiates: <300
ng/mL
Opiate
Confirmation
Oxycodone: 425
ng/mL
C
O
N
F
I
R
M
A
T
I
O
N
DEFINITIVE
Analysis
SCREENING
DEFINITIVE METHODS
• Most are immunoassaybased
• Movement to mass
spectrometry
• Targets range from specific
compounds to broad classes
– Selected to give “good
window of detection”
• Currently, mass
spectrometry
– Gas chromatography/mass
spectrometry (GC/MS)
– Liquid
chromatography/tandem
mass spectrometry
(LCMSMS, UPLCMS)
• Very specific
• Greater sensitivity
12 24 48 72
hours p ingestion
What do we mean by
specificity?
CH3
N
O
HO
CH3
N
OH
O
CH3O
MORPHINE
CODEINE
CH3
N
HO
CH3O
O
O
OXYCODONE
Cocaine assays
Opiate assays
OH
Comparison of Several IAs
Amount of drug needed to “trigger” a positive response
Calibrator
LAB IA 1
LAB IA2
lormetazepam
oxazepam
glucuronide
POCT 1
POCT 2
oxazepam oxazepam
Cut off 300 ng/mL
CLONAZEPAM
500
650
5000
500
NORDIAZEPAM
140
700
500
150
OXAZEPAM
350
3500
300
300
LORAZEPAM
890
200
4000
500
Cut-offs
• The lowest concentration of a drug
considered to be positive.
– Example: THC immunoassay 20 ng/mL; mass
spec 3 ng/mL
• Concentration depends on method and
setting.
– Clinical: Manufacturer or lab determined
based on analytical ability.
– Work place drug testing, etc: Defined by
federal or state statutes, or agency (DOT,
DOD, IOC, NFL, etc).
Examples of Cut-offs
Class
Amphetamines
Barbiturates
Benzodiazepines
Cannabinoids
Cocaine
Methadone
Opiates
Phencyclidine
target
C/O (IA)
C/O (GC/MS)
d-amphetamine/
dmethamphetamine
500
25/50/200/
500
secobarbital
200
100
diazapam/
lormetazepam
200
50/100
9COOH-THC
20
3/15
benzoylecgonine
150
50/100
methadone
300
100
morphine
2000/ 300
100
PCP
25
25
IA vs MS
In-lab IA
POCT IA
MS
Time to result
Minutes to
hours
Minutes
Hours to days
Complexity
Moderate
Waived to moderate
(to high)
High
Specificity (what is
detected)
Low to
moderate
Low
High
Sensitivity (how
much)
ng/mL
(qualitative)
ng/mL
(qualitative)
pg/mL
(quantitative)
When to use
Screening
Screening
Time sensitive
Appropriate staff and
CLIA
Screening and
confirming
Disputed screen
Screening results
unexpected
Known inability of
screen to detect drug
NOTE: NO test or method is error free.
Most errors occur before analysis (at time of collection!)
Comprehensive Testing
•
•
•
•
•
Reserve for very, selected patients
$$$$, 1-2 week tat
May need both blood and urine
Usually multiple screens followed by definitive
Examples:
– Hallucinogen panel: hallucinogens, amphetamines,
LSD, MDMD, methedrone, mescaline, PCP,
belladonna alkaloids, tryptamines, salvinorins,
phenethylamines
– Profiles to detect OTCs and prescriptives (>200
drugs)
Validity Testing
•
•
•
•
pH
Creatinine
Specific gravity
Common ‘added’ adulterants (same
old list):
– H2O; detergents, bleach, salt,
ammonia,
acids
–
–
–
–
Glutaraldehyde
Nitrites
Chromates
Peroxide and peroxidase
Interpretations
• Result below c/o
– Drug absent
– Drug present, but below
designated cut-off
– Assay does not detect drug
• Result at or above c/o
– Screen: detected drugs
belonging to the indicated
class or another similar
substance that cross-reacts
with antibody in assay
– Confirmation or definitive:
drug is present
• The result does not tell you
the route, time of, or
amount of ingestion.
Oh, NO! Unexpected
Results...
• What does the metabolic profile look
like?
– pharmacokinetics
• Was drug administered correctly, etc?
– Ex: frequency of fentanyl patch
replacement
• What other drugs are
used/prescribed, including CAMs? Use
of grapefruit, etc?
– Pharmacogenetics
– Cross-reactivity with similar compounds
(or contamination)
• Have any issues been reported with
generics? Where is the prescription
being filled?
– www.fda.gov
Oh, NO! Unexpected
Results...
• Were there any issues during
collection?
• Human error? Office or
Laboratory?
• re-test if there is any doubt
and talk to the laboratory!
Talk to YOUR LAB
• An expert is often available to help with
interpretations
• Some can be tricky – even we scratch our
heads
• Many manufacturers of screening assays
• Many versions of confirmation methods
• No two are the same
• DON’T use web based info
We are part of the health care team and
here to work with you!
Drug testing results
• Should always be used in context with other
patient data
• eg, medical record, med lists (inc old),
assessment and monitoring data, behavioral
observation, anecdotal remarks from family
• Are NOT indicative of every therapeutic
compliance scenario.
– Expert knowledge of drug metabolism and
sometimes collaboration with laboratory is
essential to an accurate interpretation
Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.
In current review
Guidelines
• National Academy of Clinical
Biochemistry – with American
Academy of Pain Management,
evidenced based
• Clinical Laboratory Standards Institute
– consensus based
• Let me know if you are interested in
reviewing……
Outline
History and use of drug testing in the clinical
setting
Who, what, when, where, how, and why
Behind the curtain – testing
• What’s in this urine?
• Your conundrums: audience submits cases
What’s in This Urine?
Case 1
• A 32 yo female with past medical history of
ADHD, anxiety, and hypothyroidism is seen for
follow-up treatment of chronic back pain of 3
years duration.
• Medication list includes
–
–
–
–
Adderall XL 30 mg po, daily
Xanax 0.5 mg po, bid
Levothyroxine 100 mcg po, daily
Percocet 5/325 mg po, 1-2 q 6 h
• What do you expect to find in her urine?
Case 1
What do you expect to find in her urine?
• Adderall – amphetamine
• Xanax – alprazolam (extensive metabolism)
• Percocet – oxycodone (oxymorphone) with
acetaminophen
• Levothyroxine – thyroxine, not monitored in urine
• Urine Drug Screens:
– Amphetamines c/o 500 ng/mL; broad specificity w
amphetamine/methamphetamine + many
sympathomimetic amines
– Benzodiazepines c/o 200 ng/mL; moderate specificity
across class, but excellent w alprazolam and metabolites
– Opiate c/o 300 ng/mL; poor specificity to oxycodone
(<1%)
Case 1
What do you expect to find in her
urine?
• Urine Drug Screen:
– Amphetamines  500 ng/mL
– Benzodiazepines  200 ng/mL
– Opiate  300 ng/mL
Do these results make sense analytically?
Are these results appropriate to prescribed medications?
Amphetamine and
Methamphetamine
•
•
Methamphetamine → amphetamine → norephedrine
Optical isomers (d- and l-)
– Illicit methamphetamine is either d- or a racemic mixture
•
Drugs containing amphetamine or methamphetamine
– Amfetamine, Adderal, benzedrine, Dexedrine, Desoxyn, Methedrine, Vick’s inhaler
•
Compounds metabolized to amphetamine or methamphetamine
– Amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine,
famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, prenylamine,
selegiline
– Methylphenidate (Ritalin) differs and often NOT detected by amphetamine immunoassays.
•
•
Isomers – not distinguished by most routine methods!
Special chromatography needed
– Look at prescribed amph/methamph (what is isomer composition?)
– > 20% d-methamphetamine is suspecious
Metabolic Profile of Opiates
OXYMORPHONE
OXYCODONE
HEROIN
HYDROMORPHONE
HYDROCODONE
6-ACETYLMORPHINE
MORPHINE
NORMORPHINE
MORPHINE
3-GLUCURONIDE
CODEINE
CODEINE
NORCODEINE GLUCURONIDE
NORMORPHINE
NORCODEINE
GLUCURONIDE
GLUCURONIDE
Metabolic Profile of Opiates
OXYMORPHONE
OXYCODONE
HEROIN
HYDROMORPHONE
HYDROCODONE
6-ACETYLMORPHINE
MORPHINE
NORMORPHINE MORPHINE
3-GLUCURONIDE
CODEINE
CODEINE
NORCODEINE GLUCURONIDE
NORMORPHINE
NORCODEINE
GLUCURONIDE
GLUCURONIDE
Metabolic Profiles of Benzodiazepines
• Alprazolam  -OH alprazolam + 4-OH
alprazolam
• Chlordiazepoxide  nordiazepam + oxazepam
• Clonazepam  7-aminoclonazepam
• Diazepam  temazepam + nordiazepam +
oxazepam
• Flurazepam  N-OH ethyl glucuronide
• Flunitrazepam  7-aminoflunitrazepam
• Lorazepam  lorazepam glucuronide
• Oxazepam  oxazepam glucuronide
• Temazepam  oxazepam
Case 1
What do you expect to find in her
urine?
• Urine Drug Screen:
– Amphetamines  500 ng/mL
– Benzodiazepines  200 ng/mL
– Opiate  300 ng/mL
Amph screen appropriate w
analytical expectations and
prescribed medications.
Results may be
appropriate.
Benzo screen has excellent
cross-reactivity with
aprazolam and its primary
metabolites. Results may
be appropriate.
Opiate screen used has
poor cross-reactivity with
oxycodone. Results
suspect.
Case 1
Confirmations ordered
• Amphetamines
– Amphetamine 3900
ng/mL
– Others < c/o
• Benzodiazepines
– OH-alprazolam 1429
ng/mL
– Others < c/o
• Opiates
– Morphine 1152 ng/mL
– Others < c/o
Are these
appropriate?
Case 1
• Amphetamine results are consistent with
prescription
• Benzodiazepine results are consistent with
prescription
• Opiate results are inconsistent with
prescription
• She subsequently admits to selling her
prescription and using heroin (last use was
several days earlier).
Case 2
• 42 yo female
• Fentanyl
• Reports lack of pain
control by day 3
• UDS ordered
– All below cut-off
• Concerned provider
calls to ask about
fentanyl detection using
screen, should
confirmation be done?
• Resident explains
fentanyl not detected
by opiate screen and
approves fentanyl
confirmation
• Confirmation is also bdl
• Now what?
Case 2 Investigation

Review of medications shows order for generic
fentanyl patch with reapplication every 5 days.

Fentanyl patch was prescribed to be changed every 5
d – timing was too long.
And at time of case, FDA recall for generic brand
used.


Recommended serum drug concentrations
 Serum fentanyl pre-application of patch shows no
detectable fentanyl.
 Serum fentanyl 24 h later within therapeutic range.
Case 3
• 53 yo male, chronic back pain
• Prescription: MS Contin 30 mg
2/d
• What do you expect in the
urine?
• UDS
– Amphetamines
<500 ng/mL
– Barbiturates <200
ng/mL
– Benzodiazepines
<200 ng/mL
– Cannabinoids 20
ng/mL
– Cocaine 150
ng/mL
– Opiates 300 ng/mL
– Methadone <300
ng/mL
Case 3
• Prescription: MS Contin 30
mg 2/d
• What do you expect in the
urine?
• UDS
– Amphetamines <500 ng/mL
– Barbiturates < 200 ng/mL
– Benzodiazepines < 200
ng/mL
– Cannabinoids  20 ng/mL
– Cocaine 150 ng/mL
– Opiates  300 ng/mL
– Methadone < 300 ng/mL
– Propoxyphene < 300 ng/mL
• Confirmation
– Opiates
•
•
•
•
•
•
•
Morphine 38540 ng/mL
Codeine <50 ng/mL
Hydromorphone 237 ng/mL
Hydrocodone <50 ng/mL
Oxycodone <50 ng/mL
Oxymorphone <50 ng/mL
6AM <15 ng/mL
– Cocaine
• Cocaine <50 ng/mL
• Benzoylecgonine 120
ng/mL
– Cannabinoids
• THC carb acid 72 ng/mL
Case 3
• Prescription:
morphine
• Confirmation
– Morphine 38540
ng/mL
– Hydromorphone 237
ng/mL
• Is this appropriate?
Cone et al J Anal Toxicol.
2008;32:319-23.
Wasan et al Pain Medicine 2008;
9:918-913
Case 3
Excretion Pattern of Cocaine and metabolites
– Where’s the cocaine?
• Cocaine
–Cocaine <50 ng/mL
–Benzoylecgonine 120 ng/mL
ng/mL
4000
BZE
EME
COC
3000
2000
1000
0
0
20
40
time (h)
60
Case 3
– Is this passive inhalation?
– Cannabinoids
• THC carb acid 72 ng/mL
Case 4
• 39 yo male with chronic low back pain following a
MVA in 2003 who returns to clinic for follow-up.
• Meds:
Lioresal (baclofen) 10 mg/po tid
Voltaren (diclofenac sodium) 1% gel topical 2-4 g 5x/d
Docusate sodium 100 mg po prn
Neurontin (gabapentin) 800 mg/po tid
Dolophine (methadone) 10 mg/po 2 morning, 1
afternoon, 1 evening, 2 bedtime
Roxicodone (oxycodone) 15 mg/po qid prn pain
Tylenol (acetaminophen) 325 mg/po 2 tab q 8 h prn
pain
What do you expect to find in his urine?
Case 4
• Screen Results 411-14
– Methadone  300
ng/mL
– Opiates < 300 ng/mL*
– Benzodiazepines < 200
ng/mL
– THC < 20 ng/mL
• Confirmation
Results
* Remember most opiate
screens do not cross-react
well with oxycodone
• Are these results consistent or
– Oxycodone < 50 ng/mL
– Oxymorphone < 50
ng/mL
inconsistent with prescribed
medications?
Case 4
Review past results
6-13
1-13
10-12
1-12
Opiates
< 300
<300
<300
<300
Methadone
 300
 300
 300
 300
Screening
Confirmation
Now what?
Oxycodone
< 50
< 50
< 50
< 50
Oxymorphone
< 50
< 50
< 50
169
Methadone
1919
1866
EDDP
2777
2453
Adulterants
unremarkable unremarkable
unremarkable
unremarkable
Could this patient have an altered
metabolic profile?
• CYP P450s, esterases, others
– Ultra-rapid metabolizers –
metabolize drugs faster than
“normal”
– Extensive metabolizers –
“normal”
– Intermediate metabolizers –
metabolize slower than
“normal”
– Poor metabolizers – metabolize
much slower than “normal”
Excretion patterns
comparing
Rapid v Poor metabolizer
12 24 48 72
hours p ingestion
Case 4
• CYP450 2D6
• Two copies of CYP 2D6*4, poor metabolizer
• CYP2D6*4 has no activity
– CYP2D6: codeine (morphine*), hydrocodone (hydromorphone*),
tramadol (o-desmethyl-tramadol), oxycodone (oxymorphone*)
– CYP3A4: codeine (norcodeine), hydrocodone (norhydrocodone),
tramadol (N-desmethyl-tramadol), fentanyl (norfentanyl)*, methadone
(EDDP), buprenorphine (norbuprenorphine)
* fentanyl, oxymorphone, morphine, hydromorphone undergo significant
1st pass metabolism
Now, what do you think of his urine drug testing results?
Case 5
• 54 yo, male
• 4 d Hx: nausea, vomiting, dyspnea, mental
status change
– Agitated, hallucinating
• PMH: cirrhosis, anemia, ETOH abuse,
hepatitis C
• Medications:
– amitriptyline, promethazine, tramadol,
hydrocodone /acetaminophen
Case 5
• Resident calls laboratory: “Can we send out a
comprehensive tox screen to look for peyote, LDS,
etc?”
• She notes that the patient has a “Combined
respiratory alkalosis and metabolic acidosis with a
prolonged PTT”
• What additional test results would you want to see
(first)?
Case 5
•
CHEM:
Na 146 (135-145)
BUN 11 (7-21)
PO4 4.3 (2.4-4.5)
K 3.5 (3.5-5.8)
CR 1 (0.8-1.4)
Mg 2.0 (1.6-2.2)
Cl 116 (98-107)
glu 87 (65-110)
AST 26 ( 19-55)
HCO3 9 (22-30)
OSMO 309
ALT 22 (19-72)
alk phos 107 (38-126)
Ca 8.2 (8.5-10.2)
GGT 27 (13126)
bili 0.3 (0-1.2)
NH4 27 (15-45)
• UA: SG 1.005; pH 5.5
• HEME: HCT 35.3 (37-51); PT 15 (12-14.4); PTT 38.3 (20.7-27.7);
INR 1.65
• ABG: pH 7.39 (7.35-7.45); pCO2 17 (35-45); pO2 108 (80-110)
• Tox: UDS neg, ETOH neg
• Referral Testing: Heavy Metals: As 20 g/d, Pb 12 g/d
• ANYTHING ELSE?
Case 5
• How about a simple salicylate level?
Case 6
• Interpret these results:
• Opiate Confirmation
– BUPRENORPHINE >40 000 ng/mL
– Norbuprenorphine < 5 ng/mL
Additional Resources
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Baselt. Disposition of Toxic Drugs and Chemicals in Man
American Academy of Pain Medicine www.painmed.org
Relieving Pain in America www.iom.edu
Reisfield, Bertholf, et al. J Opioid Manag. 2007;3:80-6.; J Opioid Manag. 2007;3:3337
Yang JM. Clin Lab Med. 2001;21:363-374.
Hammett-Stabler C, et al. Clinica Chimica Acta. 2002;315:125-135.
Cook JH, et al. J Anal Toxicol. 2000;24:579-588.
Casavant MJ. Pediatr Clin N Am. 2002;49: 317-327.
Moeller K, et al. Mayo Clin Proc. 2008;83:66-76
Cone et al. J. Anal Toxicol 2006;30:1-5
Wasan et al Pain Medicine 2008; 9:918-913
Starrels, etc al. J Gen Intern Med 27:1521–7
Radnovich, et al. Postgrad Med. 2014;126(4):59-72.
McCarberg, et al. Curr Med Res Opin. 2013;29(5):539-48.
Jannetto, et al. Expert Opin Drug Metab Toxicol. 2011;7(6):745-52.
Sehgal, et al. Pain Physician. 2012;15(3 Suppl):ES67-92
Meldrum. JAMA. 2003; 12;290(18):2470-5.
Bonezzi, et al. Minerva Anestesiol. 2012;78(6):704-11.
Kwon, et al. Pain Pract. 2013 Nov 20. doi: 10.1111/papr.12145.
Hurley, et al. Curr Opin Anaesthesiol. 2013 Aug 29.
Mantyh. Curr Opin Support Palliat Care. 2014;8(2):83-90..
Outline
History and use of drug testing in the clinical
setting
Who, what, when, where, how, and why
Behind the curtain – testing
What’s in this urine?
• Your conundrums: audience submits cases
Now for your
questions…
Drug Testing Case Studies
<11%
<2.5%
Drug Testing Case Studies
Adulterants, Substituted Specimen
• Your chronic pain patient, who is on
methadone and Provigil, hands you a urine
specimen that is less than 90oF and has a
specific gravity of <1.001 and a creatinine less
than 2.
• What do you think about this specimen?
• What do you tell the patient?
Validity Testing
•
•
•
•
•
Specific Gravity >1.001 and <1.030
Creatinine >2 mg/dl
Temperature 90° - 100°
pH > 4.5 < 9 normal range
pH absolute invalid <3 >11
Adulterants, Substituted Specimen
• Your chronic pain patient, who is on
methadone and Provigil, hands you a urine
specimen that is less than 90oF and has a
specific gravity of <1.001 and a creatinine less
than 2.
• What do you think about this specimen?
• What do you tell the patient?
Drug Testing Case Studies
Patient on Adderall for ADHD and
temazepam (Restoril) tests positive for:
Amphetamine and oxazepam (Serax)
Are the results compatible with the
legitimate prescriptions?
Office Based
Urine Drug Screening
J. Paul Martin, MD, FASAM
Medical Review Officer
https://www.communitycarenc.org/population-management/chronic-pain-project/