FORENSIC TOXICOLOGY OFFICE OF THE ARMED FORCES MEDICAL EXAMINER

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FORENSIC TOXICOLOGYOFFICE OF THE ARMED FORCES
MEDICAL EXAMINER

• JOHN JEMIONEK, Ph.D.
• CERTIFYING SCIENTIST
• DIVISION OF FORENSIC TOXICOLOGY

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DIVISON OF FORENSIC TOXICOLOGY

• MISSION
• 1) Post-Mortem and Human Performance Testing
  Laboratory
• Toxicology laboratory testing and consultation
  in medical examiner investigation and other
  special medical cases
• DoD Drug Detection Quality Assurance Laboratory
• Quality assurance oversight of the DoD Drug
  Testing Program through certification,
  proficiency testing and inspections
• 3) Forensic toxicology education and research

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LABORATORY ACCREDITATION

• American Board of Forensic Toxicology
• College of American Pathologists

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Post-Mortem and Human Performance Testing
Laboratory

• Source of Submissions
• Receive biological specimen submissions from all
  military service branches
• Office of the Armed Forces Medical Examiner
• Active duty military autopsies
• Other selected federal autopsies
• Non-Fatal Aircraft/Ground/Sea Investigations
• AFOSI, CID AND NCIS Criminal Investigations
• Fitness for Duty Investigations
• DUI/DWI Medicolegal Determinations
• Military Drug Testing Laboratories
• Other Selected Forensic Cases of National
  Interest
• For Fee MOU contributors

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Post-Mortem and Human Performance Testing
Laboratory

• Special/Non-Standard Analyses/Method Development
• Psilocin
• Ketamine
• GHB
• LSD Metabolite 2-oxo-3-OH-LSD
• Designer Amphetamines
• Ephedrine
• ?-methyl-tryptamine
• Methadone
• Method development for
• drugs of interest in response to
• military requests

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OIF/OEF Toxicology Support

• Also provide toxicology support for in theater
  non-fatal fitness for duty examinations, aircraft
  accident and criminal investigations
• Received over 3000 non-fatal cases for testing
  from OIF/OEF to date
• Received over 2500 cases from unit
  sweeps/requests for analytes not tested in the
  urine drug screening labs (i.e. benzodiazepines,
  narcotic analgesics)

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Common Drug Classes

• ANTICONVULSANTS
• ANTIBIOTICS
• ANTIDEPRESSANTS
• ANTIHISTAMINES
• BARBITURATES
• BENZODIAZEPINES
• CANNABINOIDS
• CARBON MONOXIDE
• COCAINE

• COCAINE METABOLITES
• CYANIDE
• NSAIDS/ANALGESICS
• NARCOTIC ANALGESICS
• OPIATES
• PHENCYCLIDINE
• PHENOTHIAZINES
• SYMPATHOMIMETIC AMINES
• VOLATILES

• OTHER MISCELLANEOUS DRUGS

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Commercial Product Testing

• THC content in hemp products
• Hemp oils, snack bars, Jones Juice Dave
• Coca Teas
• Mate de Coca
• Products containing ephedrine
• Thermacore RX, Xenadrine
• Clinical Quality of Care/ Pharmaceutical
  Investigations
• Adulterated products
• Morphine injector, Cisplatin IV bag,
• Horny Goat Weed

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DoD Directed Program Development

• Drug prevalence studies
• Benzodiazepines Common Rx, preliminary
  incidence 0.3 in active duty members
• 6-AM Heroin use
• Oxycodone highly abused, orally active, easy to
  obtain
• Methadone
• Ketamine

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Heroin 6 Acetylmorphine Testing
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6-Acetylmorphine Testing for Heroin Abuse
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Methadone
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Methadone Basics

• 6-(dimethylamino)-4,4-diphenyl-3-heptanone
• Synthetic Opioid Analgesic
• Schedule II Drug
• Routes of Administration oral (5-10 40 mg
  tablets or 5-10 mg liquid) and 10 mg/mL
  intravenous
• Racemic mixture

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Methadone Basics

• Names Dolophine, Methadose?, Street Meth
• Used for pain treatment and heroin dependence
• Slow pharmacokinetics, highly lipophilic, and
  high oral bioavailability
• Acute withdrawal symptoms

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Methadone

• Major metabolic pathway
• mono- and di-N-demethylation ? Unstable
  metabolites ? EDDP EMDP
• Urinary Profile
• 5-50 excreted as parent methadone
• 3-25 excreted as EDDP
• lt1 EMDP

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Methadone Use

• DAWN Estimates of ED visits
• 1997 3,832 methadone
• 2001 10,725 methadone (180 increase from 1997)
• 2004 31,874 methadone (197 increase from 2001)
• 36,559 oxycodone
• 42,491 hydrocodone
• Multiple drugs involved in 57 of cases
• DAWN does not distinguish between prescription
  and non-prescription use
• http//dawninfo.samhsa.gov/files/DAWN2k4ED.htmHig
  h4

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Prevalence Study Why?

• Prescription rate appears to be increasing
• 1998 692,675 grams of prescription methadone
  distributed
• 2001 1,892,691 grams prescription methadone
  distributed
• Establish a baseline for use/abuse in the
  military
• Oxycodone
• Evaluation of methadone and EDDP as prevalence
  markers

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Prevalence Study - Screening

• Microgenics DRI reagent ready immunoassay kits
  for methadone and methadone metabolite
• Hitachi modular P screening instrument
• 300 ng/mL calibrator Methadone/EDDP
• Assay specific and minimal cross reactivity with
  other drugs

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Prevalence Study

• 27,994 samples screened
• - AFIP DoD QA Lab and NDSL-Jacksonville
• Analyzed 25 previously confirmed methadone/EDDP
  specimens by screening and confirmation

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Results

• 5 specimens screened positive
• 2 screened positive at NDSL JAX
• 1 confirmed positive for THCCOOH
• 1 screened positive for methadone only
• confirmed negative
• 3 remaining samples confirmed positive for both
  methadone and EDDP
• 75 Confirmation rate Methadone
• 100 Confirmation rate EDDP

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Results

• 2 additional specimens screened close to cutoff
  for methadone
• Methadone screening values between 75 and 100
• EDDP screened below 75
• Both samples confirmed negative

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Prevalence Results

• Confirmation Results for the 3 positive samples
• Sample 1
• Methadone (ng/mL) 3219
• EDDP (ng/mL) 1740
• Sample 2
• Methadone (ng/mL) 1582
• EDDP (ng/mL) 1090
• Sample 3
• Methadone (ng/mL) 2304
• EDDP (ng/mL) 1624

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Methadone Prevalence Study Conclusions

• Baseline established for methadone prevalence in
  the military
• Prevalence rate is 0.01 (4 out of 27,994)
• methadone prescriptions for 2 specimens
• Methadone/EDDP screening kits are effective
• AFIP is capable of unit sweep testing for
  suspected methadone use
• If methadone availability continues to increase,
  another prevalence study may be conducted

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Ketamine
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• History

• 1960s-Developed at Parke Davis Labs while
  looking for PCP replacement, originally named
  CI1581
• 1970-FDA approval for human use
• 1970s-Patients complaining about unwanted
  visions
• 1978-1995-Social use grows
• 1995-Added to DEA emerging drug list
• 1998-1999-Labeled as a date rape drug
• August 12, 1999-Emergency Schedule III by DEA

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• Facts

• Used primarily for veterinary anesthesiology
• Used in some surgical human applications
• Slang
• The drug- K, Special K, Vitamin K, Lady K
  
• The experience-tripping, k-ing, the k- hole

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• Effects

• Dissociative anaesthetic- trance-like state
• Produces effects similar to PCP with the visual
  effects of LSD
• Does not affect breathing or circulation
• Can affect the senses, judgment, and
  coordination for 18 to 24 hours
• User feels like they are on another plane of
  existence

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• Ketamine Chemical Structure

N
O
Cl
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• Ketamine

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Ketamine Metabolites

• Over a 72 hr period, ketamine is eliminated
  primarily in the urine
• 2.3 unchanged ketamine
• 2.3 norketamine
• 16.2 dehydronorketamine
• 80 various conjugates of hydroxylated
  derivatives of ketamine.

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DoD Interest in Ketamine

• Immunoassay reagent sensitive and specific
  primarily to presence of dehydronorketamine and
  if possible norketamine and free ketamine.
• Sensitivity cutoff of 25-50 ng/ml
  dehydronorketamine.
• Confirmation GC/MS cutoff of 25 - 50 ng/ml

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Military Drug Testing FY2005 Statistical Analysis
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Impetus

• Frequently at Courts Martial, I have been asked
  about the concentration of drug detected
  especially when the drug level is 2-3 times the
  DoD confirmation cutoff level.
• While, the confirmation drug concentration may be
  moot as to a sample being called positive,
  knowing some correlates regarding drug detection
  levels may be useful.

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PURPOSE

• To determine if there is a correlation between
  the drug concentration and drug detection
  frequency as a function of the collection day.
• To determine how well the random testing software
  program is working.

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BELIEF

• I had several presumptions that I wished to
  ascertain
• First Majority of drug use occur over a weekend
• Second Urine drug collection occurs early in
  the week (Mondays) to detect weekend drug use.
• Third Drug levels would also be highest earlier
  in the week and fall off as time progressed.
• Fourth Drug use falls off during the week

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Methods

• FY 2005 USAMITC Data Base of Active Duty and
  Reserve Personnel Reported to the USAMITC Data
  Base from All Six Military Drug Testing
  Laboratories
• Monitored
• Day of the Collection Event
• Positive Drug Results
• Drug Concentration Reported

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Correlation of Percent of Samples Positive and
Percent of Samples Collected as Function of Day
of the Week
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THC Data
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THC Percent Positive Distribution by Collection
Day Normalized for the Number of Samples
Collected by Day
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THC Concentration Distribution Monday Collections
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THC Weekday Distribution Data
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Benzoylecgonine Positive Distribution by
Collection Day
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BZE Percent Positive Distribution by Collection
Day Normalized for Number of Samples Collected by
Day
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Cocaine (BZE) Weekday Distribution Data
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Amphetamine Positive Distribution by Collection
Day
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Amphetamine Percent Positive Distribution by
Collection Day Normalized for the Number of
Samples Collected by Day
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Amphetamine Weekday Distribution Data
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Methamphetamine Positive Distribution by
Collection Day
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Methamphetamine Percent Positive Distribution by
Collection Day Normalized for the Number of
Samples Collected by Day
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Methamphetamine Weekday Distribution Data
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Conclusions Randomized Testing

• Majority of samples collected and the majority of
  samples that are drug positive occur on Tuesday
  due to Monday Federal Holidays
• Randomized collections spread across the week,
  with most collection and most drug positive
  samples occurring on Monday and Tuesdays.
• There appears to be a mid-week phenomena of drug
  use Urinalysis collection already occurred on
  Monday or Tuesday and Individual not collected. ?

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Conclusions Drug Concentration and Collection
Day

• THC median drug concentrations appear to be
  evenly distributed at approximately 62 ng/ml
  independent of collection Day.
• BZE median drug concentrations appear to have a
  bi-phasic distribution with a second peak
  occurring at mid-week.
• Amphetamine median drug concentrations appear to
  be evenly distributed independent of the
  collection Day.
• Methamphetamine median drug concentration may
  have a bi-phasic distribution with a second peak
  occurring at mid-week

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Conclusion

• Drug use may not be restricted to primarily
  weekend drug use.
• There appears to be evidence of midweek drug use.
• Majority of drug positive results are in the
  lower range of concentrations encountered

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Questions?????
Contact Information Voice 301-319-0100 DSN
285-0100 Email jemionek_at_afip.osd.mil