Presentation on theme: "The Seventh Annual Providers Conference Lynnwood Convention Center Lynnwood, WA April 18, 2013 A Northwest company in the pursuit of excellence."— Presentation transcript:
The Seventh Annual Providers Conference Lynnwood Convention Center Lynnwood, WA April 18, 2013 A Northwest company in the pursuit of excellence
Unraveling the Mysteries of Urine Drug Testing Jim Heit, BS, MT(ASCP) Technical Support Manager STERLING Reference Laboratories
Unraveling the Mysteries of Urine Drug Testing COMMON TOXICOLOGY QUESTIONS
DRUG TESTING How are Drug testing results Obtained? Screening Assays – indicate the presumptive presence of drugs. Confirmation Assays – identify the drug detected in the screening assay
DRUG TESTING Immunoassay Screening tests What are they? How do they work? How accurate are they?
DRUG TESTING U + R = UR (Urine) + (Reagent) = (Reaction Product) –Appropriate reagents –Method for recognizing or measuring the reaction product
DRUG TESTING Screening Tests for Drug Class –Enzyme Immunoassay –Presumptive Presence of Drugs –Indicates the presence of a drug by recognizing that substance’s unique structure. –Relatively Inexpensive, easily automated False Positives are Possible –Essential to Confirm all POSITIVE Screens False Negatives are Rare
THE QUESTION “Paul’s explanation for his positive THC result of 45 ng/mL was because he was in his friend’s car. He wasn’t smoking but two of his buddies were.”
WEIGHT LOSS?? My client, who is very much over weight, has a history of heavy use of marijuana for many years. He recently started exercising and lost a lot of weight. He claims he tested POSITIVE for THC because THC was released from his fat cells. There is no evidence that rapid weight loss results in release of THC from adipose tissue.
CONFIRMATION ASSAYS What are the criteria? Better specificity and sensitivity than the screening test The “Gold Standard” - Gas Chromatography/Mass Spectrometry (GC/MS)
CONFIRMATION TESTING Gas Chromatography/Mass Spectrometry –Gold Standard for Confirmation –Chemical “Fingerprint” of Drugs –Sensitive and Specific –Legally Defensible Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) –Emerging Standard for Confirmation
Confirmation Testing Quantitative Results ??? –The higher the result, the more recent the use or a much larger dose of drug was used. –Debate on use of quantitative results.
THE EXCUSE My client tested POSITIVE for morphine at 739 ng/mL. He has no history of opiate abuse. He claims that he tested positive because he ate a large poppy seed muffin for breakfast on the morning of the day of the specimen collection. Poppy seeds contain morphine. Morphine levels up to 5,000 ng/mL are possible from ingestion of poppy seeds in baked goods.
WINDOW of DETECTION Depends on Drug Class Amphetamines –2 - 3 Days Cocaine –2 - 4 Days, Longer for Chronic Use Opiates –3 - 4 Days PCP –5 – 8 Days THC –Less than 2 Weeks most people –Heavy, Chronic use, up to 6 – 8 Weeks
Specimen Validity Testing Is the specimen sufficiently concentrated to interpret negative screening results? Has the specimen been tampered with or adulterated in some manner to make negative screening results invalid?
SPECIMEN VALIDITY TESTING Components Visual examination Olfactory examination Chemical Evaluation Creatinine Specific Gravity (S.G.) if creatinine is < 20 mg/dL General oxidant pH
SPECIMEN VALIDITY TESTING Dilution –Creatinine <20 mg/dL Inert metabolite from skeletal muscle, concentration dependent on hydration status Most sensitive indicator of dilution –Specific Gravity <1.003 Measurement of dissolved solids Determined only if Creatinine <20 mg/dL
SPECIMEN VALIDITY TESTING There is ABSOLUTELY NOTHING that can be taken by mouth, except WATER or other fluids, that will produce a Negative Urine Drug Test. Excessive fluid intake results in Low Creatinine levels.
THE QUESTION So what is the big deal about a dilute specimen? Why should I care that it is dilute?
THE QUESTION I received the report that said that the urine was “dilute”. How much water did the person drink?
URINE SPECIMEN DILUTION Pre-Collection Dilution consumption of large quantities of fluids prior to collection Post-Collection Dilution adding fluid to specimen at the time of collection
PRE-COLLECTION DILUTION High-volume ingestion of fluids (water loading, flushing, hydrating, etc.) Flushing or detoxifying products –Gold Seal, Clean ‘n Clear, Test-Free, etc No evidence these products have any additional effect on drug elimination
SPECIMEN VALIDITY TESTING Medical Causes for Dilute Urines Diabetes Insipidus Anorexia Nervosa or other muscle wasting syndromes Kidney Disease Diuretics Pharmaceutical Toxicity Lithium, others
SPECIMEN VALIDITY TESTING pH Testing – SAMHSA Guidelines Acceptable pH: 4.5 to 9.0 SAMHSA Guidelines for Adulteration: ≤3.0 or ≥11.0 SAMHSA Guidelines for Invalid Result: >3.0 to 9.00 to <11.00
SPECIMEN VALIDITY TESTING Iodine Producing Adulterants (Urine Luck 6.5) Strong Acid and Fluorine (Urine Luck 6.3 and 6.4) Chromium VI (various formulations of PCC and potassium dichromate) Peroxidase/Peroxide (Stealth) Bleach Nitrite (Klear, Whizzies) NaCl (table salt)
EXAMPLES Creatinine <1 mg/dL Specific Gravity pH 7.8 Interpretation – Creatinine <2.0, specific gravity acceptable –Actual results from an artificial urine encountered frequently in Northern WA
SPECIMEN VALIDITY TESTING Substitution is now more prevalent than adulteration Quick Fix Clear Test Ultra Pure
WHIZZINATOR AD Available in a variety of natural lifelike skin tones Fully adjustable latex belt 4 oz vinyl bag One dehydrated, toxin free urine specimen Four organic heat pads $150.00
SPECIMEN VALIDITY TESTING Synthetic Urine –Mimics normal human urine Creatinine Electrolytes (Na,K, Cl, Ca, Mg) Urea, Phosphate –Difficult to detect by standard testing Depends on knowledge and skill of chemist Non-Human Urine –Difficult to Detect
SYNTHETIC URINE Is it legal to make or sell synthetic urine? YES Is it Illegal to substitute synthetic urine? –In most states NO WA has no statute –Illegal in ten states PA, TX, NE, NC, SC, NJ, VA,OR, MD, AL
ARTIFICIAL URINE TEST STERLING has found a unique analyte that is lacking in synthetic urine. Five Synthetic Urines Purchased –12 Components Screened –3 Compounds Studied –1 Analyte Chosen Missing in all synthetic urines studied. Unobserved Employment Urines Screened –5.7% of 567 specimens synthetic urine
ALCOHOL TESTING Blood or Breath Alcohol –Gold Standard –Legally Defined Limit of Impairment –12 Hour Window of Detection Urine Alcohol –Does not correlate with Blood Alcohol –14 Hour Window of Detection –Fermentation is Potential Problem
ALCOHOL TESTING Ethylglucuronide –Direct Bio-Marker of Ethanol Exposure –Stable, Water Soluble –Minor Metabolite of Ethanol –Synthesis in Liver EtOH +glucuronic acid = EtG –Window of Detection 72 – 96 Hours Dependent on amount and frequency of consumption –No False Positives –Fermentation NOT a Factor
ETHYLGLUCURONIDE Not a marker of impairment –Does not correlate with BAC Not a marker for amount of alcohol consumption
ETHYLGLUCURONIDE: ANALYSIS Screening Assays –LC/MS/MS –Immunoassay Confirmation Assays –LC/MS/MS EtS Detected and Quantified No False Positives Legally Defensible
ETHYLGLUCURONIDE Voluntary Exposure to Ethanol –Voluntary consumption of alcoholic beverage Incidental Exposure to Ethanol –Alcohol exposure without intent Not a FALSE POSITIVE Result –Alcohol exposure in both situations
ETHYLGLUCURONIDE SAMHSA Advisory Analytical Methods are Valid! What are Appropriate Cut-Offs? Interpretation of Low Positive Results? Incidental Exposure?
THE EXCUSE “My job requires me to wash dirty car parts in denatured alcohol. Every 20 – 30 minutes I have my hands in the alcohol. That is why my EtG level was 2600 ng/mL”
ETHYLGLUCURONIDE CUT-OFFS Common Positive Cut-Off Values 100 ng/mL –Used in “zero tolerance” programs –Susceptible to incidental exposure 250 ng/mL –Used in most programs –Less susceptible to incidental exposure 500 ng/mL –Used in more “liberal/tolerant” programs –Least susceptible to incidental exposure
Alternate Matrices Hair Oral Fluid On Site Devices
HAIR ADVANTAGES Provides a longer estimate of time of drug use Observed collection Ease of obtaining, storing, and shipping specimens Second specimen can be obtained from original source
HAIR DISADVANTAGES Recent use not detected Casual user may not be detected Possible hair type biases Possible false positives from external contamination Expensive
ORAL FLUID ADVANTAGES Gender neutral collections Non-invasive collection Detects recent use Possible correlation with state of impairment
ORAL FLUID DISADVANTAGES Short window of detection Quality of specimen is collection device dependent Specimen recovery from stimulant abusers difficult Drug recovery, especially cocaine, is pH dependent Limited test menu
Onsite Devices Advantages Instant Results Ability to confront donor May be cheaper Disadvantages Qualitative results and subjective interpretation No accurate cut-offs High false positive rate Specimen validity tests unreliable
Others Sweat Patches Finger/toe nails Skin scrapings Meconium
SPICE and BATH SALTS Calls to Poison Control Centers SPICE – ,870 calls about spice –Jan calls 2011 Projected = 4,620 – ,890 actual calls BATH SALTS – calls about bath salts –Jan calls 2011 Projected = 3,012 – actual calls
SPICE: Synthetic Cannabinoids Synthetic cannabinoids started out as legitimate scientific endeavors. More than 250 synthetic cannabinoids synthesized.
SPICE: HISTORY 2004 First Appearance in Europe 2008 Wide Spread use in Europe 2008 First Appearance in United States 2008 First Analysis of SPICE at University of Freiburg, Germany 2009 Wide Use in United States 2010 Laboratory Testing of Spice Available
SPICE: Preparation Botanical MaterialHerbal Incense Synthetic cannabinoids sprayed on herbs, allowed to dry Residual solvent No quality control Batches inconsistent Expensive compared to marijuana Caveat emptor
SPICE: Pharmacology Euphoria (“high”) similar to Marijuana Relaxation Altered state of consciousness Distortion of sensory experiences Impaired motor control Increased reaction time Decreased cognition NO effect on appetite
SPICE: Adverse Side Effects Elevated Blood Pressure Increased Heart Rate Hyperventilation Anxiety and Agitation Paranoia Seizures Vomiting Death (unsubstantiated media reports)
SPICE: International Legal Status All or some Synthetic Cannabinoids Banned AustraliaAustria FranceGermany Japan New Zealand PolandRomania RussiaSlovak Republic South KoreaSwitzerland United Kingdom
SPICE: Legal Status in U.S. States Some or all Synthetic Cannabinoids Banned AlabamaArkansas GeorgiaIllinois IowaKansas KentuckyLouisiana MichiganMissouri Nevada (?)New Hampshire New MexicoOklahoma OregonTennessee Utah (?)Washington West Virginia
SPICE: Legal Status U.S. Military Banned in All Branches of Military –U.S. Army –U.S. Air Force –U.S. Coast Guard –U.S. Marine Corps –U.S. Navy
SPICE: Legal Status U.S. Federal Schedule Status November 24, 2010 DEA published in Federal Register intent to place five synthetic cannabinoids on Schedule 1 of CSA. March 1, 2011 final rule published. STATUS: Schedule 1, therefore ILLEGAL
SPICE: Laboratory Testing Synthetic Cannabinoids not detected in THC screening immunoassays or THC confirmatory GC/MS testing. Immunoassays now available. On-Site screening tests now available, but high cutoff severely limits usefulness. LC/MS/MS technology available. Few labs perform testing. Expensive $30 - $100 per sample
SPICE: ANALYSIS Future of Spice Testing –More compounds to be tested as SPICE formula evolves. –New metabolites. Alternative Matrix –Blood Measure Parent Drug –Oral Fluid Measure Parent Drug –Hair Enhanced Window of Detection
DESIGNER DRUGS: BATH SALTS
CATHINONES Fresh leaves chewed or consumed as tea Originated in Ethiopia Causes release of dopamine from brain areas Sale of Khat legal in - Australia by permit Oman Yemen United Kingdom
DESIGNER DRUGS: Bath Salts Central Nervous System Stimulants Similar in action to methamphetamine Thought to be highly addictive MDPV is 5–8x potency of methylphenidate Available as research chemical in 2007 Popular in Europe and Australia Legal –Banned in Louisiana and Florida Jan. 2011
BATH SALTS: Adverse Side Effects Elevated Heart Rate and Blood Pressure Anxiety and agitation Hallucinations Extreme Paranoia Delusions Seizures Nausea and Vomiting Death
BATH SALTS: ANALYSIS Bath Salts are not detected in Amphetamine Screening Immunoassays or Confirmatory GC/MS assays Immunoassays available, but expensive. Rapid On-Site Tests not available LC- or GC/MS assays available for MDPV and Others Available at STERLING March 1, 2011
SPICE and BATH SALTS FUTURE OF DESIGNER DRUGS They are here to stay. The problem will get worse long before it gets better. DEMAND = SUPPLY Analytical Labs Will Always Lag Behind the Synthetic Chemists