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INTERPRETATION OF DRUGTESTING RESULTSBert Toivola, Ph.D.Laboratory Director
INTERPRETATION OF DRUG TESTING RESULTSSANTA CLARA COUNTYSEPTEMBER 14, 2018SAN JOSE, CALIFORNIAPage 2
AGENDA Screening Tests Confirmation Tests Specimen Validity Tests Case Reports Novel Psychoactive Drugs Aka Designer Drugs
INTERPRETATION OF DRUG TESTING RESULTSCourtesy of Jeremy ShinodaPage 4
SCREENING TESTS FIRST LINE TEST (SENSITIVE NOT SPECIFIC) DESIGNED TO IDENTIFY NEGATIVE SPECIMENS DRUGS Methadone Ethanol DRUG METABOLITE Benzoylecgonine THC-COOH FAMILY OF DRUGS Amphetamines Benzodiazepine Barbiturates OpiatesPage 5
CONFIRMATORY TESTING LIQUID CHROMATOGRAPHY /TANDEM MASSSPECTROMETRY (LC/MS/MS) LIQUID CHROMATOGRAPHY Separates analytes of interestTANDEM MASS SPECTROMETRY Detection method for analytes of interest Molecular mass and fragmentation patternPage 6
CONFIRMATORY TESTING DESIGNED TO IDENTIFY POSITIVE SPECIMENS TEST PERFORMED THAT EMPLOYS PHYSICAL-CHEMICALPROPERTIES DISTINCTLY DIFFERENT FROM THESCREENING TEST. SENSITIVE AND SPECIFIC ACCEPTABLE METHODOLOGIES GC/MS, GC/GC/MS, GC/MS/MS LC/MS, LC/MS/MS UNACCEPTABLE METHODOLOGIES ALTERNATE FORMAT IMMUNOASSAY RIA, FPIA, ELISAPage 7
TANDEM MASS SPECTROMETERWATERS XEVO TQD MASS SPECTROMETER WITH ACQUITYLIQUID CHROMATOGRAPHY SYSTEMPage 8
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INTERPRETATION OF DRUG TESTING RESULTSCocaine MetaboliteBenzoylecgoninePage 14
OPIATES AND OPIOIDS OPIATES Naturally occurring substances Codeine Morphine OPIOIDS Synthetic or semi-synthetic substances Heroin Hydrocodone, hydromorphone Oxycodone, oxymorphone Fentanyl, meperidine, tramadol, Methadone, buprenorphinePage 15
OPIATES AND OPIOIDS OPIUM PAPAVER SOMNIFERUM ALKALOIDS Codeine Morphine Thebaine HISTORICAL USE Medicinal RecreationalPage 16
OPIATES AND OPIOIDS SOURCES OF MORPHINE Codeine Morphine Heroin Poppy Seeds 2,000 ng/mLPage 17
OPIATES AND OPIOIDS HEROIN SYNTHESIZED IN 1874 Objective More potent analgesicagent than morphine Less addictive thanmorphinePage 18
OPIATES AND OPIOIDSPage 19
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BENZODIAZEPINESSEDATIVE –HYPNOTIC CLASS OF DRUGSCNS DEPRESSANTS SEDATIVE Anxiolytic Effect Reduce Anxiety Alcohol or Opiate withdrawal Calming Effect HYPNOTIC Produce Drowsiness Induce Sleep ANTI-SEIZUREPage 26
BENZODIAZEPINESLEGAL BENZODIAZEPINES IN THE UNITED STATES Chlordiazepoxide (Librium) Nordiazepam * Oxazepam * Clorazepate (Tranzene) Nordiazepam * Oxazepam * Alprazolam (Xanax) Alpha OH Alprazolam * Lorazepam (Ativan) Lorazepam *Page 27
BENZODIAZEPINESLEGAL BENZODIAZEPINES IN THE UNITED STATES Triazolam (Halcion) Alpha OH Triazolam * Midazolam (Versed) Alpha OH Midazolam * Flurazepam (Dalmane) 2 OH Ethylflurazepam * Clonazepam (Klonopin) 7 Amino Clonazepam *Page 28
BENZODIAZEPINESLEGAL BENZODIAZEPINES IN THE UNITED STATES Estazolam (Prosom) Quazepam (Doral) Clobazam (Onfi)Page 29
BENZODIAZEPINESILLEGAL BENZODIAZEPINES IN THE UNITED STATES FLUNITRAZEPAM (ROHYPNOL) “Date rape drug” 7-Amino Flunitrazepam * PHENAZEPAM Developed in Russia Spiked into “Spice” in New ZealandPage 30
BENZODIAZEPINESETIZOLAMINDICATED FOR USE IN INSOMNIAANXIOLYTIC, ANTICONVULSANT, HYPNOTIC, SEDATIVE,MUSCLE RELAXANTNOT FDA APPROVED FOR USE IN USANOT A CONTROLLED SUBSTANCE BY DEASCHEDULED IN ALABAMA, ARKANSAS, FLORIDA,MISSISSIPPI, VIRGINIA, TEXAS, LOUISIANA, GEORGIA,ARIZONA AND INDIANAAVAILABLE VIA INTERNETPage 31
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ETHYLGLUCURONIDEAlcohol is the most abused drugIt is also the most difficult to monitorabstinencePage 35
ETHYLGLUCURONIDE ETHANOL METABOLISM OXIDATION – 95% Acetaldehyde Acetate DIRECT – 5 % Breath Urine Perspiration MINOR METABOLITES - 0.1% Ethylglucuronide (EtG) Ethylsulfate (EtS)Page 36
ETHYLGLUCURONIDE: BIOMARKERSThe Old EraDIRECT BIOMARKERS (SENSITIVE AND SPECIFIC) Blood or Breath Alcohol Legally Defined (0.08 %) 8 – 12 Hour Window of Detection Urine Alcohol 12 – 14 Hour Detection Window Fermentation Potential ProblemPage 37
ETHETHYLGLUCURONIDELGLUCURONIBIOMARKERSThe New Era DIRECT BIOMARKERS (SENSITIVE AND SPECIFIC) Ethylglucuronide (EtG) Ethylsulfate (EtS)Page 38
ETHYLGLUCURONIDE: BIOMARKERSPage 39
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ETHYLGLUCURONIDEEtG versus Time10000000EtG ng/mL10000001,081,91EtOH 84 mg/dLEtOH 40 mg/dL100000100001000100104/1/204/ 088/24/ 0015 8/24/ 0022 8/4/ 20029 8/205/ 086/25/ 0013 8/25/ 0020 8/25/ 0027 8/206/ 083/26/ 0010 8/26/ 0017 8/26/ 0024 8/207/ 081/20081DateData collected at SRL, Tacoma, WA by Toivola et. al.Page 42
INTERPRETATION OF DRUG TEST Specimen Validity Testing Is the specimen sufficiently concentrated to interpret negativescreening results? Has the specimen been tampered with or adulterated in somemanner to produce negative screening tests?Page 43
INTERPRETATION OF DRUG TESTRESULTS SPECIMEN VALIDITY TESTING Creatinine 20.0 mg/dL Specific gravity 1.0030 – 1.0300 Only measured if creatinine 20.0 mg/dL pH 4.5 – 8.9 Nitrite 500 μg/mLPage 44
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CREATININE AND DILUTE URINEWHAT IS THE SIGNIFICANCE OF A LOW CREATININELEVEL ?A LOW CREATININE LEVEL IS CONSISTENT WITH A DILUTESPECIMEN!DILUTE URINE HAS AN EXCESSIVE AMOUNT OF WATER!DRUGS, WITH THE EXCEPTION OF ETHANOL, ARE DILUTEDTO THE SAME DEGREE AS CREATININEINTERPRETATION OF NEGATIVE SCREENING TEST RESULTSARE INVALID IN DILUTE URINE!Page 47
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THC/CREATININE RATIOPage 51
THC/CREATININE RATIO III-APage 52
THC/CREATININE RATIO III-APage 53
CONFIRMATION TESTINGWINDOW OF DETECTIONAMP/METH2-3 DAYSCOCAINE2-5 DAYSOPIATES3-5 DAYS6-AM12-16 HOURSMETHADONE4-7 DAYSTHC1-4 WEEKSBENZODIAZEPINES2-14 DAYSBARBITURATES2-14 DAYSPage 54
BEST PRACTICES IN TOXICOLOGYConcentrationDrug Elimination CurvePOSITIVE CUTOFFTime0Page 55
DESIGNER DRUGSCURRENT STATE OF DESIGNER DRUGSSYNTHETIC CANNABINOIDS (SPICE)SYNTHETIC CATHINONES (BATH SALTS)GABAPENTINKRATOMSYNTHETIC OPIOIDS AND FENTANYLSPage 56
SPICEThis is your grandmother’sParsley, Sage, Rosemary and ThymePage 57
SPICEThis is not your grandmother’sParsley, Sage, Rosemary and ThymePage 58
DESIGNER DRUGSPage 59
DESIGNER DRUGSCALLS TO POISON CONTROL CENTERS SPICE 20102,915 calls 20116,890 calls 20125,228 calls 20132,668 calls 20143,595 calls 20157,779 calls 20162,695 calls 20171,950 calls 2018 (6/30/2018)1,114 callsPage 60
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DESIGNER DRUGS SYNTHETIC CANNABINOIDS RCS-4 AKB-48 AB-PINACA 5F-AB-PINACA AB-FUBINACA ADBICA 5F-ADBICAPage 62
DESIGNER DRUGSBATH SALTS EPSOM SALTS OR SEA SALT, OR BOTH BAKING SODA 1 OR 2 TEASPOONSOF GLYCERIN (OPTIONAL) ESSENTIAL OILS – MANDARINORANGE, LAVENDER,SANDLEWOOD AND PATCHOULIPage 63
DESIGNER DRUGS: BATH SALTSPage 64
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DESIGNER DRUGSCALLS TO POISON CONTROL CENTERS BATH SALTS 2010303 calls 20116,137 calls 20122,691 calls 2013995calls 2014582calls 2015522calls 2016428 callsPage 66
DESIGNER DRUGSBATH SALTS: ADVERSE SIDE EFFECTS Elevated Heart Rate and Blood Pressure Anxiety and agitation Hallucinations Extreme Paranoia Delusions Seizures Nausea and Vomiting DeathPage 67
DESIGNER DRUGSSYNTHETIC CATHINONES (BATH SALTS NAPHYRONE FLEPHEDRONE METHEDRONE 4F-METHCATHINONE 4F-METHAMPHETAMINE DMAA Alpha-PVP (flakka, gravel)Page 68
DESIGNER DRUGSAlpha-PVP (alpha-pyrrolidinopentiophenone)Increase blood pressure and heart rateExtreme hyperthermiaHallucinationsParanoid DelusionsBouts of rage with extreme strengthPage 69
GABAPENTINGABAPENTIN (NEURONTIN) FDA APPROVED MEDICAL USES ANTI-SEIZURE (GABA AGONIST?) ANALGESIC (NON-OPIOID) SHINGLES POST HERPETIC NEURALGIAPage 70
GABAPENTINNON FDA APPROVED USESALCOHOL AND COCAINE WITHDRAWALDIABETIC NEUROPATHYRESTLESS LEG SYNDROMEFIBROMYALGIAHYPERHIDROSISPage 71
GABAPENTINDRUG OF ABUSE ?NOT A CONTROLLED SUBSTANCELOW ADDICTIVE OR ABUSE POTENTIALPSYCHOACTIVE AT HIGH DOSESHIGH SIMILAR TO THC?WITHDRAWAL SYMPTOMS SIMILAR TO OPIOIDWITHDRAWALUSED AS CURRENCY IN PRISONPage 72
DESIGNER DRUGS KRATOM Mitragyna speciosa Indigenous to SE Asia Mitragynine 7-OH Mitragynine Sedative at low doses Opioid at higher doses Legal DEA-drugs of concern listPage 73
KRATOMKratom, which is made using an Asian plant, isn’t “just aplant”, the FDA says—it’s an opioid.If it looks like an opioid and acts like an opioid, it’s an opioid.Page 74
KRATOMPage 75
KRATOMPage 76
BENZODIAZEPINESDESIGNER ONAZEPAMCROSS REACT IN SCREENING TESTS, BUT CONFIRMATORYTESTS NOT AVAILABLEPage 77
OPIOIDSPage 78
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FENTANYLANALGESIC50 – 100 X POTENCY OF MORPHINESTIMULATES MU OPIOID RECEPTORRAPID ONSET, SHORT ACTINGPREPARATIONS (SCHEDULE II)DERMAL PATCH (DURAGESIC )I.V. SOLUTION (SUBLIMAZE )LOLLIPOPSLOZENGES, NASAL SPRAYPage 81
FENTANYLMEDICAL USESANESTHESIA AND ANALGESIA COMBINEDWITH PROPOFOL OR MIDAZOLAMCHRONIC PAIN MANAGEMENTRECREATIONAL USEOPIOID OR HEROIN SUBSTITUTESPIKED INTO HEROINPage 82
MORPHINE & FENTANYL LETHAL DOSEPage 83
FENTANYLADVERSE EFFECTSRESPIRATORY DEPRESSIONPage 84
DESIGNER DRUGSFENTANYL ANALOGSMore potent than morphineSpiked into heroinNumerous deaths reportedPage 85
FENTANYL ANALOGSHeroin10 x morphineFentanyl50-100 x morphineAcetylfentanyl 10 x morphineCarfentanil10,000 x morphineValerylfentanyl 1-5 x morphine (?)Furanylfentanyl 5-10 x morphine (?)Butrylfentanyl 10-25 x morphine (?)Page 86
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SYNTHETIC OPIOIDSLegitimate investigational pharmaceuticalsU-477007.5 x morphineAH-79210.8 x morphineMT-451 x morphinePage 88
DextromethorphanDissociative at high dosesPage 89
Loperamide Imodium A DDiphenoxylate LomotilPage 90
btoivola@cordanths.comBTOIVOLA@CORDANTHS.COMPage 91
Sep 14, 2018 · Legal DEA-drugs of concern list DESIGNER DRUGS. Page 74 KRATOM. Kratom, which is made using an Asian plant, isn’t “just a plant”, the FDA says—it’s an opioid. If it looks like an opioid and acts like an opioid, it’s an opioid. Page 75
