Download Overview of Drug Testing g g Methods

Overview of Drug
g Testing
g
Methods
Anthony Albanese,
Albanese M
M.D.
D
Clinical Associate Professor of
y
y
Medicine & Psychiatry
UC Davis Medical School
Director, Chemical Dependency &
H
Hepatology
t l
P
Programs
Sacramento VA Medical Center
DISCLAIMER
• No financial interests to disclose
(UNFORTUNATELY)
Commonly asked liver
questions
• Is it safe to use naltrexone in HCV
patients? – Black box..but yes in non
decompensated pt
pt. if you monitor LFT’s
LFT s.
• Is it safe to use statins in patients will
alcoholic liver disease or hep c? … yes in
non decompensated pt. if you monitor
LFT s.
LFT’s
• Monitoring interval? Baseline, 1 week,
1 month,
th 4 months
th
Prevalence of HCV in Select Populations
Illicit drug users
~ 300,000
((80%–90%))2,3
Alcoholics
~ 240,000
(11%–36%)5
Incarcerated
~ 330,000 to 860,000
(16%–41%)1
Female
Male
HIV-infected
~ 300,000
(30%)4
Homeless
~ 175,000 (22%)7
37%
63%
Veterans
~ 280,000 (8%)8
Living below poverty
level ~ 940,000
(3.2%)6
Children
(6–18 years old)
~ 100,000 (0.1%)9
Adapted
Ad
d ffrom: 1
1. CDC
CDC. MMWR.
MMWR 2003;52(RR-1):1-33;
2003 52(RR 1) 1 33 2
2. Edli
Edlin B
B. Hepatol.
H
t l 2002;36(5
2002 36(5 suppll 1)
1):S210-S219;
S210 S219 3
3. NHSDA R
Report 2003
2003;
4. Poles M, et al. Clin Infect Dis. 2000;31:154-161; 5. LaBrecque D, et al. Hepatitis C Choices. 2002:7-15; 6. Alter M, et al. N Engl J
Med. 1999;341:556-562; 7. Nyamathi A, et al. J Gen Intern Med. 2002;17:134-143; 8. Bräu N, et al. Am J Gastroenterol.
2002;97:2071-2078; 9. Jonas M. Hepatol. 2002;36(5 suppl 1):S173-S178.
OBJECTIVES
• Discuss role of Medical Review Officers
(MRO)
• Discuss limitation of screening test
• Review options for forensic testing
• Discuss the role of drug testing in the
treatment of addictive disease
Brief History
• 1981 – US Department of Defense instituted periodic
and random drug testing of all servicemen.
• 1984 – Nearly 80% Fortune 500 companies were
conducting pre-employment drug testing.
• 1988 – Resulting from Executive Order# 12564, and
congressional public law # 11-71 Department of Health
and Human Service Guidelines published- require a
licensed physician to be responsible – MRO’s’ are
born!, DOT involved by 1989.
Swotinsky,R, et al. J. Occ Med;
32;10;1990 pp 1003-1008
Why Do We Need MRO’s?
MRO s?
• To protect the rights of the prospective
employee ( not a patient).
• To protect the interests of the prospective
employer – the client.
• To
T oversee and
d review
i
th
the iintegrity
t it off th
the
forensic testing procedure.
• To pursue life, liberty, happiness, and
justice for all!
How ?
4 of the “NIDA
NIDA 5”
5 drugs tested have
legitimate uses
• Cocaine
• Dronabanol- anti nausea,
appetite stimulant
• TACTAC topical anesthetic,
anesthetic
vasoconstrictor
• Opiates
• Pain relief – not 6-MAM
• Amphetamines
• Depression, ADHD,
narcolepsy
• No legitimate use
• Marijuana
• Phencyclidine (PCP)
Furthermore……
Screening tests can yield false positive
results ( less common in 3rd EMIT)
• Amphetamine- ephedrine, pseudoephedrine,
phenylephrine, selegiline, chlorpromazine, trazodone,
buproprion amantadine
buproprion,
amantadine, ranitidine
ranitidine, fluoxitine
• Marijuana
j
– Ibuprofen,
p
, naproxyn,
p y , efavirenz,, protonix
p
promethazine, tolectin
• OpiatesO i t
Rifampin, Flouroquinolones, quinine, poppy
seeds, chlorpromazine, dolobid
Medical Letter Vol 44, August
10,2002
Screening
g tests can yyield false
positive results
• Phencyclidine- Ketamine, Dextromethorphan,
Venlafaxine, diphenhydramine, meperidine
• Cocaine – coca leaf tea, ? Others ?
• Alcohol- in urine, yeast + sugar = EtOH
• http://www.askdocweb.com/falsepositives.html
Common Screening Methods:
Immunoassay
• Radioimmunoassayy ((RIA)) & Enzyme-Linked
y
Immunosorbent Serologic Assay (ELISA) –
heterogeneous assays
• Enzyme
y
Immunoassayy (EIA)
(
) or Enzyme
y
Multiplied Immunoassay Technique (EMIT),
Cloned Enzyme Donor Immunoassay (CEDIA) –
detect certain wavelengths of light when enzyme links antigen drug to
antibodytib d homogeneous
h
assays.
• Fluorescence Polarization Immunoassay
(FPIA)- Based on competitive binding of labeled and unlabeled antigen
t the
to
th antibody
tib d complex
l
• Kinetic Interaction of Microparticles in Solution
(KIMS)– latex microspheres coated with drug and cause turbidity when
Ab added
dd d unless
l
d
drug concentration
t ti in
i sample
l inhibits
i hibit agglutination.
l ti ti
The Gold Standard
Confirmatory test
• Gas chromatography/
g p y mass
spectroscopy (GC/MS)
• Liquid chromatography/ mass
spectroscopy ( LC/MS)
• Chromatography separates
compounds & detects isomers
• Mass spectroscopy uses electron
impact
pact o
or cchemical
e ca ionization
o at o to
identify the compound.
Concentration determined by
determining ratio of tested drug to
internal standard.
Testing
g Methods
• Urine- accepted as the standard for the “5” drugs but
not alcohol.
alcohol Accepted for DOT and government
workers/contractors. GC/MS confirmation available.
Problems include adulteration, dilution, “shy bladder”.
I
Inexpensive
i - ~ $15/ ttestt
• Oral Fluid- not yet accepted for DOT/government
applications.
li ti
LC/MS confirmation
fi
ti available.
il bl All
collections observed. Less problem with adulteration.
Cost ~ $30/test
• Sweat – not yet accepted for most applications. Patch
worn for 24hr then read. Confirmation tests more difficult.
TIME TABLE for
Ui d
Urine
drug screening
i
Test drug
+ test
Amphetamine
1000 ng/ml
duration
2-3 days
Methamphetamine 500 ng/ml
Amphetamine
500 ng/ml
Cocaine
300ng/ml
2-3 d up to 8 d
Marijuana
50 ng/ ml
1-7 d up to 30d
Opiates
*2000/15,000 ng/ml
1-3 days
Phencyclidine
25 ng/ml
7-14 days
The Medical Letter Vol 44
(W1137A) August 19, 2002
Hair Testing
g
• Head hair g
grows about ½ inch/month. Hair
testing can give a record of use over a period of
months, not days.
• Tests
T
can be
b confirmed
fi
db
by GC/MS
GC/MS.
• There is some question of ethnic bias as dark
hair concentrates metabolites better than light
hair.
pe s e ~ $
$150-200/test
50 00/test – “onezees”
o e ees
• Expensive
available.
• Not approved for DOT/ government.
Collection Process (Urine testing)
• D
Donor iis positively
iti l id
identified
tifi d with
ith photo
h t ID
by collector and asked to remove outer
garments
t and
d leave
l
purse or b
briefcase.
i f
List of current meds requested.
• Donor washes hands, enters bathroom
with no running water and “bluing” in toilet.
Provides sample ( ~45 ml ) into container.
• Collector insures temp is 90 -100 F and
places sample in specimen bottles (30ml &
15ml) and seals them. Donor signs tape &
lab slip, before changing.
Collection Process (Urine testing)
Shy Bladder”
Bladder
“Shy
• Donor must provide 45ml of urine for a
valid test
test. If unable
unable, may be given up 40 oz
of water (1.2 liters) over a period of 3 hrs.
• If no pre-existing
i ti medical
di l condition
diti tto
explain reason, MRO reports “refusal to
t t” If short
test”.
h t term
t
conditionditi
“
“cancelled”
ll d”
• If permanent or long-term condition noted
& this is pre-employment, return to duty or
f/u test, clinical hx and physical must be
performed for evidence of illicit drug use.
Lab testing
g ((Urine))
• Collector signs lab slip gives specimen to
courier Lab officer signs slip
courier.
slip, ensuring
intact “chain of custody”.
• Specimen is tested for creatinine
creatinine, specific
gravity (SG), pH, and adulterants.
• Possible adulterants include nitrites
nitrites,
hexivalent chromium, halogens,
glutaraldehyde,
g
y , surfactants and other
oxidizing agents.
Interfering Medications (Urine testing)
•
•
•
•
•
Amiodarone
Ciprofloxacin
Gi
Griseofulvin
f l i
Mefenamic Acid
Metronidazole
• Salicyluric Acid
(metabolite of ASA)
• Sulfasalazine
• Sulindac
• Tolmentin
Lab Testing (Urine)
• Creatinine < 20mg/dl but > 2 mg/dl is a
dilute sample and requires SG test
• SG > 1
1.0010
0010 but < 1
1.0030
0030 is a dilute
specimen.
• Creatinine
C ti i < 2
2mg/dl
/dl and
d SG < 1
1.0010
0010 or
SG > 1.020 is a substituted specimen.
• Creatinine < 2 & SG >1.0010 and <1.020
or creatinine > 2 & SG < 1.0010 are
invalid specimens
Lab Testing (Urine - pH)
• pH < 3 or >11 is an adulterated specimen
• pH > 3 & < 4.5 or >9.0 and < 11 is an
invalid specimen.
specimen Urine (with bacteria)
store higher than room temp can produce
ammonia and raise pH
pH.
• For pH 9.0-9.5 -MRO must discuss with
d
donor
tto see if there
th
is
i an explanation.
l
ti
MRO may report result, cancel, or cancel
and
d requestt di
directt observation
b
ti retest.
t t
Reporting
p
g Process
• Negative samples reported to MRO review
company as such.
h P
Positive
iti specimen
i
confirmed by GC/MS or LC/MS.
• MRO makes
k a reasonable
bl effort
ff t tto contact
t t
donor. After positive identification,
discusses result
result, looking for medical
explanation and intact chain of custody.
Donor may request retest (of sample “B”B
at own expense- $ fronted by employer).
• Reports finding as positive, negative,
canceled, unsuitable, or adulterated.
MRO Interview
“Essential Elements”
1 Contact –Donor
1.
Donor generally has ~ 72 hrs to
get back to MRO after initial contact
attempt If no contact MRO informs
attempt.
employer of need to contact donor.
2 MRO identifies self
2.
self, and obtains positive
ID from Donor.
3 MRO informs
3.
i f
Donor
D
off results
lt and
d
records spontaneous comments.
MRO Interview
“Essential Elements”
4 Miranda Information “ I need to let you know that
4.
I am the MRO, not your physician. The information you
give me may not be kept confidential.”
5. Discuss collection process and chain of
y
custody.
6. Elicit information to determine whether
there is a medical explanation for the
result
7 Offer Retest Rights – don
7.
don’tt delay initial
report to company if retest requested.
MRO Interview
Interview- no contact
1. Donor declines interview – report
p result
2. MRO can not reach donor. MRO informs
Designated Employer Representative
(DER) of need to contact. Donor has 72
hrs to contact MRO.
3. MRO and DER can’t reach donor. MRO
may report result after 10 days
days.
Department
p
of Transportation
p
(DOT) 49 CFR 40
• Federal Aviation Administration ( FAA)
• Federal Motor Carriers Safety
Administration (FMCSA)
• Federal Railroad Administration (FRA)
• Federal Transit Administration (FTA)
• Coast Guard
• Government Contractors
(DOD DOE,
(DOD,
DOE NASA,
NASA NRC)
www.dot.gov/ost/dapc/
Department of Transportation
(DOT) 49 CFR 40
• DOT has established “safety
safety sensitive
sensitive”
positions (pilot vs baggage handler).
• MRO must still report results as per
protocol, but may issue a “safety issue”
letter of concern depending on
circumstances.
• www.dot.gov/ost/dapc/
d t
/ t/d
/ for
f regulations
l ti
What next ?
• A lost chance for employment may be a
prime
i
opportunity
t it for
f a brief
b i f intervention.
i t
ti
• In some “Drug Free Workplace”
environments (hospitals), pre-employment
“positives” must be referred to the state
board or diversion program.
• Donors must be referred to a substance
abuse professional (SAP). This may be
through
g the company
p y EAP.
MRO vs SAP
• SAPs are generally licensed physicians,
social workers, or psychologists who
evaluate and treat addictive illness.
• Beware of conflicting roles if you’re
program
p
g
is contracted for SAP duties with
a corporation for whom you are acting as
an MRO.
Drug Testing in Hospitals &
Addiction Treatment Programs
• Important to obtain biological confirmation
of the history.
• Offers Clinician the opportunity to provide
immediate feedback to patient.
• Provides
P id b
basis
i ffor th
therapeutic
ti iintervention
t
ti
when indicated.
• Validation of Sobriety .
Drug Testing in Hospitals &
Addiction Treatment Programs
• Important to realize that results are often
followed by comment “for medical purposes
only” – indicating no chain of custody, and no
confirmatory testing.
• Many facilities use the 2nd generation screening
tests (for cost savings) so false positives occur –
primarily with amphetamines, PCP, MJ, opiates,
and benzos
benzos.
• OK to ask pts about positive results, but confirm
test results with GC/MS ( on sample in lab)
before being confrontational.
Questions & Discussion