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Drugs of Abuse TestingDrugs of Abuse Testing

Dr Julia ChangDr Julia ChangChemical PathologistChemical Pathologist

QML PathologyQML PathologyNov 15, 2011Nov 15, 2011

Where does drug testing Where does drug testing ““pop uppop up””

in in medical practice?medical practice?

DrugDrug--rehab programs, suspected overdose or rehab programs, suspected overdose or misusemisuse

Suspected drink spikingSuspected drink spiking

Mum finds Mum finds ““tablettablet””

in sonin son’’s rooms room

Occupational testing Occupational testing ––

random, incidentrandom, incident--related, related,

prepre--employmentemployment

CourtCourt--ordered testingordered testing

DoCSDoCS--ordered testingordered testing

Sports drug testing Sports drug testing (Australian Sports Anti(Australian Sports Anti--Doping Authority )Doping Authority )

Choice of SamplesChoice of Samples

BloodBlood

Least usedLeast used

Relatively short detection intervalRelatively short detection interval

UrineUrine

AS/NZS 4308AS/NZS 4308

Detection interval approx. within the 3Detection interval approx. within the 3--4 days prior to sample collection4 days prior to sample collection

Oral FluidOral Fluid

AS 4760AS 4760

Detection interval generally 3 to 12 hours after last useDetection interval generally 3 to 12 hours after last use

HairHair

Review of past drug use of 6 or even 12 months prior to sample cReview of past drug use of 6 or even 12 months prior to sample collectionollection

Oral Fluid Drug TestingOral Fluid Drug Testing

AS 4760AS 4760

Four classes of drugs:Four classes of drugs:

OpiatesOpiates

AmphetamineAmphetamine--type stimulantstype stimulants

CannabisCannabis

Cocaine and metabolitesCocaine and metabolites

Detection interval generally 3 to 12 hours after last use Detection interval generally 3 to 12 hours after last use (close to the period for which performance could be (close to the period for which performance could be impaired) impaired)

Technology is relatively immature Technology is relatively immature

Hair Drug AnalysisHair Drug Analysis

Review of past drug use of 6 or even 12 Review of past drug use of 6 or even 12 months prior to sample collectionmonths prior to sample collection

Currently testing through Forensic Science Currently testing through Forensic Science South AustraliaSouth Australia

ANALYTICAL METHODSANALYTICAL METHODS

liquid chromatography/mass spectrometryliquid chromatography/mass spectrometry

Drugs detected by Forensic Science SA Drugs detected by Forensic Science SA

BenzodiazepinesBenzodiazepinesNitrazepam, 7aminonitrazepam, clonazepam, 7aminoclonazepam, flunNitrazepam, 7aminonitrazepam, clonazepam, 7aminoclonazepam, flunitrazepam, itrazepam, 7aminoflunitrazepam, bromazepam, clobazam, triazolam, alprazolam7aminoflunitrazepam, bromazepam, clobazam, triazolam, alprazolam, lorazepam, temazepam, , lorazepam, temazepam, diazepam, nordiazepam, midazolam, oxazepam) diazepam, nordiazepam, midazolam, oxazepam)

Zopiclone, zolpidemZopiclone, zolpidem

OpiatesOpiatesMorphine, codeine, 6Morphine, codeine, 6--monoacetylmorphine, diacetylmorphine (heroin),monoacetylmorphine, diacetylmorphine (heroin),pethidine, methadone, fentanyl, oxycodone.pethidine, methadone, fentanyl, oxycodone.

KetamineKetamine

Sympathomimetic aminesSympathomimetic aminesAmphetamine, methylamphetamine, 3,4Amphetamine, methylamphetamine, 3,4--methylenedioxymethamphetamine (MDMA)methylenedioxymethamphetamine (MDMA)

Cocaine and benzoylecgonine.Cocaine and benzoylecgonine.

d9d9--tetrahydrocannabinol (d9tetrahydrocannabinol (d9--THC)THC)

Hair Drug Analysis Hair Drug Analysis ––

““GapsGaps””

A number of drugs are still undetectableA number of drugs are still undetectable

Other considerations:Other considerations:

Passive or environmental positivesPassive or environmental positives

Effect of washing of the sampleEffect of washing of the sample

Effect of bleaching and dyeing Effect of bleaching and dyeing

Nature of exposure required to return a positiveNature of exposure required to return a positive

Relative affinity of different drugs for hairRelative affinity of different drugs for hair

Urine Drug TestingUrine Drug Testing

AS/NZS 4308AS/NZS 4308

Detection interval approx. within the 3Detection interval approx. within the 3--4 days 4 days prior to sample collection prior to sample collection

AS/NZS 4308:2008AS/NZS 4308:2008

Class of drugClass of drug

Amphetamine type substancesAmphetamine type substances

BenzodiazepinesBenzodiazepines

Cannabis metabolitesCannabis metabolites

Cocaine metabolitesCocaine metabolites

OpiatesOpiates

CutCut--off levelsoff levels

Levels at or above which the drug test is regarded as Levels at or above which the drug test is regarded as ““positivepositive””

and below which the drug test is regarded as and below which the drug test is regarded as

““negativenegative””

To minimise false positive and historical positive tests To minimise false positive and historical positive tests

Urine Drug Testing Urine Drug Testing

Immunoassay:Immunoassay:Thresholds differ from Country to CountryThresholds differ from Country to Country

Recommended by: Recommended by: Standards Australia SAMHSA (2002)Standards Australia SAMHSA (2002)(AS/NZS 4308)(AS/NZS 4308)

CannabinoidsCannabinoids

5050

5050

Cocaine metabolitesCocaine metabolites

300300

150150

Sympathomimetic AminesSympathomimetic Amines

300300

500500

OpiatesOpiates

300300

20002000


200200

PhencyclidinePhencyclidine

2525

10

Urine Drug Testing ProcessUrine Drug Testing Process

A twoA two--step processstep process

The screening test The screening test ––

immunoassay and thin layer immunoassay and thin layer chromatography (TLC)chromatography (TLC)

The confirmatory test The confirmatory test ––

mass spectrometry eg mass spectrometry eg GC/MS, LC/MS/MSGC/MS, LC/MS/MS

Screening Test Screening Test ––

Immunoassay Immunoassay

Use antibodies to detect the presence or absence of a Use antibodies to detect the presence or absence of a class of drugs in the sample class of drugs in the sample

Antibodies recognise a specific fragment on the drug Antibodies recognise a specific fragment on the drug molecule molecule

Generally a Generally a ““classclass””

methodmethod

OpiatesOpiates


Amphetamine type substances Amphetamine type substances

CocaineCocaine


Screening Test Screening Test ––

Immunoassay Immunoassay

LimitationsLimitations

Specificity Specificity

Unable to distinguish drugs in the same class eg codeine Unable to distinguish drugs in the same class eg codeine and morphineand morphine

CrossCross--reactivityreactivity

Unable to distinguish substances that are therapeutically Unable to distinguish substances that are therapeutically unrelated but chemically similar eg unrelated but chemically similar eg ranitidine and THCranitidine and THC

NonNon--negative tests should be viewed as negative tests should be viewed as presumptivepresumptive

Screening Test Screening Test --

TLCTLC

The testing is based on the The testing is based on the differences in the migration rate differences in the migration rate of various substances through a of various substances through a porous supporting mediumporous supporting medium

The degree of migration and the The degree of migration and the colour are characteristic of colour are characteristic of certain drugscertain drugs

SemiSemi--quantitative estimation quantitative estimation

Detect more than 100 drugs eg Detect more than 100 drugs eg some antisome anti--depressants, antidepressants, anti--

psychotics etcpsychotics etc

Confirmation Testing Confirmation Testing

Gas chromatography/mass spectrometry Gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) spectrometry (LC/MS)

Identify a specific compound by its Identify a specific compound by its characteristic fingerprint (mass spectrum)characteristic fingerprint (mass spectrum)

Specific and sensitive but more timeSpecific and sensitive but more time--consuming consuming and technically complexand technically complex

Not subject to the interferences associated with Not subject to the interferences associated with the immunoassay testthe immunoassay test

Interpretation of ResultsInterpretation of Results

False positive results (immunoassay only) False positive results (immunoassay only)

Zoloft may produce nonZoloft may produce non--negative initial benzodiazepine drug screens negative initial benzodiazepine drug screens

Innocent positive results Innocent positive results

Some overSome over--thethe--countercounter--medications containing pseudoephedrine may medications containing pseudoephedrine may produce nonproduce non--negative sympathomimetic amine initial drug screens negative sympathomimetic amine initial drug screens

Historical positive resultsHistorical positive results

Lipophilic property Lipophilic property --

cannabinoids, benzodiazepinescannabinoids, benzodiazepines

A confirmed positive result does not provide information onA confirmed positive result does not provide information on

The amount of drug ingestedThe amount of drug ingested

The exact time of ingestionThe exact time of ingestion

The frequency of ingestionThe frequency of ingestion

Whether an individual was Whether an individual was ““under the influenceunder the influence””

at the time of sample at the time of sample collectioncollection

DRUGS OF ABUSEDRUGS OF ABUSE--INITIAL IMMUNOASSAY SCREENINITIAL IMMUNOASSAY SCREEN

Urinary thresholUrinary thresholds specifiedds specifiedin AS/NZS 430in AS/NZS 4308:20088:2008

Cannabinoids POSITIVE 5Cannabinoids POSITIVE 50 ug/L *0 ug/L *Cocaine metabolites Negative 30Cocaine metabolites Negative 300 ug/L *0 ug/L *Sympathomimetic Amines Negative 30Sympathomimetic Amines Negative 300 ug/L0 ug/LOpiates Negative 30Opiates Negative 300 ug/L0 ug/LBenzodiazepines Negative 20Benzodiazepines Negative 200 ug/L0 ug/LCreatinine 1.3 mmol/LCreatinine 1.3 mmol/LSample Collection temperature 35 degrees CSample Collection temperature 35 degrees CRecent Medication History NilRecent Medication History Nil

The Chain of Custody form has been inspected. Together The Chain of Custody form has been inspected. Together with thewith theresults from the adulterant screen, the temperature and results from the adulterant screen, the temperature and thethesupervision of the collection suggest adulteration of thsupervision of the collection suggest adulteration of the samplee sampleafter passage is unlikely.after passage is unlikely.

The urine was very dilute. This suggests a large water The urine was very dilute. This suggests a large water intake prior intake prior to passage of the urine, or perhaps adulteration of the to passage of the urine, or perhaps adulteration of the sample with sample with water after collection. This may be used to dilute out water after collection. This may be used to dilute out any drug any drug metabolites to concentrations below detection limits. metabolites to concentrations below detection limits.

Urinary Creatinine Urinary Creatinine

••

Normal product of muscle metabolismNormal product of muscle metabolism

••

Concentration determined by the amount of Concentration determined by the amount of muscle in the subjectmuscle in the subject’’s body and the amount of s body and the amount of water that his kidneys are excreting at the time water that his kidneys are excreting at the time of sample collectionof sample collection

••

There is a (usually) minor contribution from dietThere is a (usually) minor contribution from diet

••

An indicator of the overall concentration of the An indicator of the overall concentration of the samplesample

Urinary Creatinine Urinary Creatinine

••

Average concentrationAverage concentration••

1010--12 mmol/L in males12 mmol/L in males••

88--10 mmol/L in females10 mmol/L in females

••

““Usual rangeUsual range””••

5 5 ––

15 mmol/L15 mmol/L••

May indicate dilution in some individualsMay indicate dilution in some individuals••

0.44 0.44 ––

1.76 mmol/L1.76 mmol/L••

Not consistent with human urineNot consistent with human urine••

Less than 0.44 mmol/L Less than 0.44 mmol/L

Urine Drug TestingUrine Drug Testing

An Adulterated Specimen An Adulterated Specimen ••

A urine specimen containing a substance that is A urine specimen containing a substance that is not a normal constituent or containing an not a normal constituent or containing an endogenous substance at a concentration that is endogenous substance at a concentration that is not a normal physiologic concentrationnot a normal physiologic concentration

Presenter

Presentation Notes

Adulteration Adulteration

Diluted urineDiluted urine

To dilute substances in the sample to a level below To dilute substances in the sample to a level below the threshold for detectionthe threshold for detection

Household chemicals Household chemicals

Bleach, table salt, detergent, vinegar etcBleach, table salt, detergent, vinegar etc

Commercially available products Commercially available products

Klear Klear (potassium nitrite)(potassium nitrite), Urine Luck , Urine Luck (PCC)(PCC),,

Stealth Stealth (Peroxidase and hydrogen peroxide) (Peroxidase and hydrogen peroxide) etcetc

Note Note ––

adulterant checks do not detect sample adulterant checks do not detect sample

substitutionsubstitution


““MarijuanaMarijuana””

––

dried material of Cannabis sativadried material of Cannabis sativa

Most frequently used illicit drugMost frequently used illicit drug

> 60 C> 60 C2121

compoundscompounds

ΔΔ99--tetrahydrocannabinol (THC)tetrahydrocannabinol (THC)

Lipophilic propertyLipophilic property

Chronic users Chronic users ––

positive test up to 6 weeks positive test up to 6 weeks

Light users Light users ––

positive test for 3positive test for 3--4 days4 days


When smokedWhen smoked

Physiologic and psychologic effects for 3 to 4 hoursPhysiologic and psychologic effects for 3 to 4 hours

Impaired motor performance for up to 24 hoursImpaired motor performance for up to 24 hours

Multiple potential medicinal use e.g. treatment of Multiple potential medicinal use e.g. treatment of nausea, cancernausea, cancer--

or HIVor HIV--associated cachexia etc. associated cachexia etc.

Generally considered as a soft drug BUTGenerally considered as a soft drug BUT

Chronic cannabis syndrome Chronic cannabis syndrome

Associated with increased prevalence of Associated with increased prevalence of schizophrenia and depressionschizophrenia and depression

A 25 year old employee of a mining company returned a A 25 year old employee of a mining company returned a positive urine drug screen. He stated that he had positive urine drug screen. He stated that he had attended a party on the previous evening that several attended a party on the previous evening that several friends had smoked cannabis during the evening. friends had smoked cannabis during the evening.

DRUGS OF ABUSEDRUGS OF ABUSE--INITIAL IMMUNOASSAY SCREENINITIAL IMMUNOASSAY SCREENUrinary thresholUrinary thresholds specifiedds specified

in AS/NZS 430in AS/NZS 4308:20088:2008Cannabinoids POSITIVE 50 ug/L Cannabinoids POSITIVE 50 ug/L **Cocaine metabolites Negative 30Cocaine metabolites Negative 300 ug/L *0 ug/L *Sympathomimetic Amines Negative 30Sympathomimetic Amines Negative 300 ug/L0 ug/LOpiates Negative 30Opiates Negative 300 ug/L0 ug/LBenzodiazepines Negative 20Benzodiazepines Negative 200 ug/L0 ug/LCreatinine 8.6 mmol/LCreatinine 8.6 mmol/LSample Collection temperature 35 degrees CSample Collection temperature 35 degrees CRecent Medication History NilRecent Medication History Nil


GCMS ASSAY GCMS ASSAY -- URINE THC CONFIRMATIONURINE THC CONFIRMATIONDate Lab No d9Date Lab No d9--THCA U.Creat RatioTHCA U.Creat Ratio

ug/L mmol/Lug/L mmol/L------------------------------------------------------------------------------------------------------------------------------------

02/11/08 1718821 > 300 8.6 > 3502/11/08 1718821 > 300 8.6 > 35

d9d9--THCA: 11 nor delta tetrahydrocannabinolTHCA: 11 nor delta tetrahydrocannabinol--99--carboxylic acidcarboxylic acid(assayed according to AS/NZS 4308:2008 requirements)(assayed according to AS/NZS 4308:2008 requirements)The AS/NZS 4308:2008 cutThe AS/NZS 4308:2008 cut--off for this compound is 15 ug/L.off for this compound is 15 ug/L.

1718821 D91718821 D9--THCA calculated result based on extrapolation above highestTHCA calculated result based on extrapolation above higheststandard was approximately 2264 ug/L (ratio: approx. 263).standard was approximately 2264 ug/L (ratio: approx. 263).

GCMS confirms the initial finding of cannabinoids at a levelGCMS confirms the initial finding of cannabinoids at a level above theabove theStandards Australia threshold for reporting results as "posiStandards Australia threshold for reporting results as "positive".tive".

GCMS confirms the positive cannabinoid screen and reveals the prGCMS confirms the positive cannabinoid screen and reveals the presence of esence of a large amount of d9a large amount of d9--THCA in this urine. This finding is suggestive of THCA in this urine. This finding is suggestive of use within 24 hours prior to sample collection if the subject isuse within 24 hours prior to sample collection if the subject is an an occasional user. However, if the subject is a heavy longoccasional user. However, if the subject is a heavy long--term user who term user who has recently ceased use, this result may be seen up to one week has recently ceased use, this result may be seen up to one week after after cessation. cessation.

Dr Julia ChangDr Julia Chang

A 46 year old employee of a transportation companyA 46 year old employee of a transportation companyreturned a positive urine cannabinoid screen. Hereturned a positive urine cannabinoid screen. Hedenied use of any illicit drugs. denied use of any illicit drugs.

DRUGS OF ABUSEDRUGS OF ABUSE--INITIAL IMMUNOASSAY SCREENINITIAL IMMUNOASSAY SCREENUrinary thresholUrinary thresholds specifiedds specified

in AS/NZS 430in AS/NZS 4308:20088:2008Cannabinoids POSITIVE 50 ug/L Cannabinoids POSITIVE 50 ug/L **Cocaine metabolites Negative 30Cocaine metabolites Negative 300 ug/L *0 ug/L *Sympathomimetic Amines Negative 30Sympathomimetic Amines Negative 300 ug/L0 ug/LOpiates Negative 30Opiates Negative 300 ug/L0 ug/LBenzodiazepines Negative 20Benzodiazepines Negative 200 ug/L0 ug/LCreatinine 9.5 mmol/LCreatinine 9.5 mmol/LSample Collection temperature 35 degrees CSample Collection temperature 35 degrees CRecent Medication History NilRecent Medication History Nil


On further questioning, the subject revealed using hempseedOn further questioning, the subject revealed using hempseedoil as salad dressing. oil as salad dressing.

GCMS ASSAY GCMS ASSAY -- URINE THC CONFIRMATIONURINE THC CONFIRMATIONDate Lab No d9Date Lab No d9--THCA U.Creat RatioTHCA U.Creat Ratio

ug/L mmol/Lug/L mmol/L------------------------------------------------------------------------------------------------------------------------------------

02/11/08 1718821 36 9.5 3.802/11/08 1718821 36 9.5 3.8

d9d9--THCA: 11 nor delta tetrahydrocannabinolTHCA: 11 nor delta tetrahydrocannabinol--99--carboxylic acidcarboxylic acid(assayed according to AS/NZS 4308:2008 requirements)(assayed according to AS/NZS 4308:2008 requirements)The AS/NZS 4308:2008 cutThe AS/NZS 4308:2008 cut--off for this compound is 15 ug/L.off for this compound is 15 ug/L.

GCMS confirms the initial finding of cannabinoids at a levelGCMS confirms the initial finding of cannabinoids at a level above theabove theStandards Australia threshold for reporting results as "posiStandards Australia threshold for reporting results as "positive".tive".

CocaineCocaine

18851885

––

CocaCoca--Cola was named Cola was named for its two for its two ““medicinalmedicinal””

ingredients: extract of coca ingredients: extract of coca leaves and kola nutsleaves and kola nuts

Coke used to contain about Coke used to contain about 0.75 mg of cocaine per ounce0.75 mg of cocaine per ounce

Cocaine was removed in 1903 Cocaine was removed in 1903 because of increasing reports because of increasing reports of adverse effects, such as of adverse effects, such as stroke and cardiac arreststroke and cardiac arrest

CocaineCocaine

A strong CNS stimulantA strong CNS stimulant

Cocaine hydrochloride is legally available for use Cocaine hydrochloride is legally available for use as a local or topical anaesthetic as a local or topical anaesthetic

Routes of administrationRoutes of administration

Sniffing or snorting, injecting and smokingSniffing or snorting, injecting and smoking

Main metabolites Main metabolites

Benzoylecgonine and ecgonine methylester Benzoylecgonine and ecgonine methylester

Detection Times (Benzoylecgonine)Detection Times (Benzoylecgonine)

Positive for two to three days Positive for two to three days

Chronic heavy use Chronic heavy use ––

positive up to two weekspositive up to two weeks

A 24 year old footballer returned a positive urine A 24 year old footballer returned a positive urine

cocaine screen.cocaine screen.

GCMS ASSAY GCMS ASSAY -- URINE COCAINE METABOLITES CONFIRMATIONURINE COCAINE METABOLITES CONFIRMATION

Cocaine Cocaine NDNDBenzoylecgonine Benzoylecgonine 1313 ug/L *1313 ug/L *Ecgonine Methyl Ester Ecgonine Methyl Ester 63 ug/L63 ug/LCreatinine Creatinine 8.6 mmol/L8.6 mmol/L

(ND = Not detected, D = Detected)(ND = Not detected, D = Detected)

Assayed to AS/NZS 4308:2008 requirements.Assayed to AS/NZS 4308:2008 requirements.The cutoff level is 150 ug/L for both Benzoylecgonine and EcgoThe cutoff level is 150 ug/L for both Benzoylecgonine and EcgoninenineMethyl Ester. The standard does not stipulate a cutMethyl Ester. The standard does not stipulate a cut--off for Cocaine.off for Cocaine.

1718821 GCMS confirms the positive cocaine screen and reveal1718821 GCMS confirms the positive cocaine screen and reveals a patterns a patternof recent use of cocaine.of recent use of cocaine.

Dr Julia ChaDr Julia Chang ng


Chemically and pharmacologically related to naturally Chemically and pharmacologically related to naturally occurring epinephrine and norepinephrineoccurring epinephrine and norepinephrine

Amphetamine, methamphetamine, phentermine, and the Amphetamine, methamphetamine, phentermine, and the structurally related structurally related ““designerdesigner””

drugs, e.g. MDMA (Ecstasy)drugs, e.g. MDMA (Ecstasy)

CNS stimulantsCNS stimulants

Increase wakefulness and suppress appetite, Increase wakefulness and suppress appetite,

Increased energy, selfIncreased energy, self--confidence, wellconfidence, well--being and euphoriabeing and euphoria

Amphetamine is used clinically for treatment of Attention Amphetamine is used clinically for treatment of Attention Deficit Disorder with Hyperactivity (ADHD)Deficit Disorder with Hyperactivity (ADHD)

Amphetamine is the metabolite of selegiline Amphetamine is the metabolite of selegiline (antiparkinsonian)(antiparkinsonian)


Detection timesDetection times

3 to 4 days (urinary pH change the concentration in 3 to 4 days (urinary pH change the concentration in urine)urine)

False Positives False Positives

Some Some ““overover--thethe--countercounter””

nonnon--prescription prescription medications eg pseudoephedrinemedications eg pseudoephedrine

SelegilineSelegiline

Following an accident at the workplace, a 28 year old male Following an accident at the workplace, a 28 year old male forklift driver was required to provide a sample of urine for thforklift driver was required to provide a sample of urine for the e

purposes of drug testing. purposes of drug testing. Recent medication history Recent medication history –– Cold and Flu medication.Cold and Flu medication.

MS ASSAY MS ASSAY -- URINE SYMPATHOMIMETIC AMINES CONFIRMATIONURINE SYMPATHOMIMETIC AMINES CONFIRMATIONCutCut--off levelsoff levels

Amphetamine 131 ug/L 150 ug/LAmphetamine 131 ug/L 150 ug/LMethamphetamine 99 ug/L 150Methamphetamine 99 ug/L 150 ug/Lug/LMDMA Not Detected 150MDMA Not Detected 150 ug/Lug/LMDA Not Detected 150MDA Not Detected 150 ug/Lug/LPhentermine Not Detected 500Phentermine Not Detected 500 ug/Lug/LEphedrine Not Detected 500Ephedrine Not Detected 500 ug/Lug/LPseudoephedrine 953 ug/L 500 ug/LPseudoephedrine 953 ug/L 500 ug/LCreatinine 19.3 mmol/LCreatinine 19.3 mmol/L

Assayed to AS/NZS 4308:2008 requirements.Assayed to AS/NZS 4308:2008 requirements.

Mass spectroscopy confirms the positive sympathomimetic Mass spectroscopy confirms the positive sympathomimetic amine screen and amine screen and reveals a pattern consistent with the recent use of pseureveals a pattern consistent with the recent use of pseudoephedrine. Mass doephedrine. Mass spectroscopy also reveals a small amount of methamphetamspectroscopy also reveals a small amount of methamphetamine and amphetamine. ine and amphetamine. However, as neither the amphetamine nor methamphetamine However, as neither the amphetamine nor methamphetamine reached the reached the threshold specified in the Standard, this cannot be regathreshold specified in the Standard, this cannot be regarded as a positive rded as a positive confirmation for medicolegal purposes.confirmation for medicolegal purposes.

I would recommend repeating the test in the hope of achiI would recommend repeating the test in the hope of achieving a moreeving a moredefinitive result.definitive result.


Presenter

Presentation Notes

OpiatesOpiates

What makes you thinkI’ve been using drugs?

OpiatesOpiates

Alkaloid compounds extracted from opium poppyAlkaloid compounds extracted from opium poppy

Morphine and codeineMorphine and codeine

Semisynthetic derivatives eg heroin, hydrocodone, oxycodoneSemisynthetic derivatives eg heroin, hydrocodone, oxycodone

Analgesic and CNS depressant effects Analgesic and CNS depressant effects

Codeine metabolismCodeine metabolism

Heroin (diacetylmorphine) MetabolismHeroin (diacetylmorphine) Metabolism

Duration of action Duration of action

44--5 hours5 hours

HalfHalf--lifelife

Heroin Heroin ––

3 to 20 minutes 3 to 20 minutes

66--monoacetylmorphine monoacetylmorphine ––

9 to 40 minutes9 to 40 minutes

Morphine Morphine ––

1 to 7 hours1 to 7 hours

The Effect of Consumption of Poppy Seed on The Effect of Consumption of Poppy Seed on Urinary Opiates Urinary Opiates

(Courtesy of Dr Charles Appleton)(Courtesy of Dr Charles Appleton)

For the purposes of defining whether consumption of For the purposes of defining whether consumption of poppy seed was capable of producing a nonpoppy seed was capable of producing a non--negative negative opiate result, a volunteer consumed a "slightly opiate result, a volunteer consumed a "slightly heaped"heaped"

teaspoon of poppy seed.teaspoon of poppy seed.

This was consumed without other foodstuffs other This was consumed without other foodstuffs other than approximately 300 mL of coffee containing milk than approximately 300 mL of coffee containing milk but no sweetener.but no sweetener.

Consumption of the poppy seed commenced at 12:30 Consumption of the poppy seed commenced at 12:30 hrs and took place over approximately 10 minutes.hrs and took place over approximately 10 minutes.

Samples of urine and oral fluid were collected at 13:00 Samples of urine and oral fluid were collected at 13:00 hrs, 14:00 hrs and 15:30 hrs.hrs, 14:00 hrs and 15:30 hrs.

Urinary Findings After Consumption of Poppy Seed Urinary Findings After Consumption of Poppy Seed (Courtesy of Dr Charles Appleton)(Courtesy of Dr Charles Appleton)

TimeTime

Oral fluidOral fluid

UrineUrineCCreat.reat.

Morphine Morphine CodeineCodeine30 mins30 mins

negneg

19.519.5

negneg

negneg90 mins90 mins

40 (Morphine)40 (Morphine)

6.46.4

184184

42423 hours3 hours

35 (Morphine)35 (Morphine)

17.017.0

376376

5757

Poppy seed is capable of producing an innocent positive opiate Poppy seed is capable of producing an innocent positive opiate screen in the urinescreen in the urine

The codeine in the urineThe codeine in the urine

was approximately 20% of the morphine was approximately 20% of the morphine level level

Typically codeine constitutes between 5% to 20% of the morphine Typically codeine constitutes between 5% to 20% of the morphine found in the urine after consumption of poppy seedfound in the urine after consumption of poppy seed

However there is a However there is a high codeine high codeine variety of poppy seeds for culinary variety of poppy seeds for culinary use use ––

more codeine than morphine detected in urine more codeine than morphine detected in urine

Onsite random urine drug testing, the Onsite random urine drug testing, the collector noted the abnormal colour and collector noted the abnormal colour and

abnormal creatinine reading. Temperature was abnormal creatinine reading. Temperature was not registered. A recollection was done.not registered. A recollection was done.

GCMS ASSAY GCMS ASSAY -- URINE OPIATE CONFIRMATIONURINE OPIATE CONFIRMATIONDate Lab No Codeine Morphine U.Creat Cod/CreDate Lab No Codeine Morphine U.Creat Cod/Crea Mor/Creaa Mor/Crea

(ug/L) (ug/L) (mmol/L) Rati(ug/L) (ug/L) (mmol/L) Ratio Ratioo Ratio

Assayed to AS/NZS 4308:2008 requirements.Assayed to AS/NZS 4308:2008 requirements.The cutoff level for both Codeine and Morphine is 300ug/L.The cutoff level for both Codeine and Morphine is 300ug/L.

1907905 No urine creatinine was detected. The sample does 1907905 No urine creatinine was detected. The sample does not appear tonot appear tobe genuine urine.be genuine urine.


The specimen donor states that he took pain killers The specimen donor states that he took pain killers including Neurofen Plus for severe tooth problemsincluding Neurofen Plus for severe tooth problems

GCMS ASSAY GCMS ASSAY -- URINE OPIATE CONFIRMATIONURINE OPIATE CONFIRMATIONDate Lab No Codeine Morphine U.Creat Cod/CreDate Lab No Codeine Morphine U.Creat Cod/Crea Mor/Creaa Mor/Crea

(ug/L) (ug/L) (mmol/L) Rati(ug/L) (ug/L) (mmol/L) Ratio Ratioo Ratio

17/11/08 1907909 1576 > 2000 3.0 5217/11/08 1907909 1576 > 2000 3.0 525 > 6675 > 667

GCMS confirms the positive opiate screen and also reveals the prGCMS confirms the positive opiate screen and also reveals the presence ofesence ofa small amount of 6a small amount of 6--monoacetyl morphine (13 ug/L). The presence ofmonoacetyl morphine (13 ug/L). The presence of66--monoacetyl morphine is indicative of probable use of heroin withmonoacetyl morphine is indicative of probable use of heroin withinineight hours of sample collection.eight hours of sample collection.Additional to this, the subject appears to have used a codeiAdditional to this, the subject appears to have used a codeinene--containingcontainingmedication as well. This may be done in an attempt to "mask"medication as well. This may be done in an attempt to "mask" the use ofthe use ofheroin but the presence of 6heroin but the presence of 6--MAM defeats this.MAM defeats this.


PoppyPoppy--Seed DefenceSeed Defence

A 43 year old lady undertaking urine drug tests for the A 43 year old lady undertaking urine drug tests for the custody proceeding custody proceeding

History of opiate and alcohol dependence, and History of opiate and alcohol dependence, and depressiondepression

Current medications includeCurrent medications include

Alprazolam (benzodiazepine)Alprazolam (benzodiazepine)

Lexapro (antidepressant)Lexapro (antidepressant)

Lamictal (anticonvulsant)Lamictal (anticonvulsant)

Suboxone (opiate dependence) Suboxone (opiate dependence)

URINE DRUG SCREENURINE DRUG SCREEN 23/3/1123/3/11

Urine Creatinine Urine Creatinine 4.5 mmol/L4.5 mmol/L

Urine AlcoholUrine Alcohol None detectedNone detected

Urine Alcohol (Mass units) Urine Alcohol (Mass units) < 10 mg%< 10 mg%

< 0.01 g% < 0.01 g%

Urine TemperatureUrine Temperature 36.0 degrees C.36.0 degrees C.

Drugs that were detected by thin layer chromatography screen: Drugs that were detected by thin layer chromatography screen: Phentermine Phentermine

Nicotine and metabolites of nicotineNicotine and metabolites of nicotine

Drugs that were detected by immunoassay:Drugs that were detected by immunoassay:

OpiatesOpiates


*****Updated Report 24/03/2011**********Updated Report 24/03/2011*****

The specific buprenorphine immunoassay confirms the presence ofThe specific buprenorphine immunoassay confirms the presence of

buprenorphine (Suboxone) in this urine. GCMS confirmation for buprenorphine (Suboxone) in this urine. GCMS confirmation for

The Opiate findings to follow.The Opiate findings to follow.


MS ASSAY MS ASSAY --

URINE BENZODIAZEPINES CONFIRMATION URINE BENZODIAZEPINES CONFIRMATION 23/03/1123/03/11

Oxazepam Oxazepam Not DetectedNot Detected

Temazepam Temazepam Not DetectedNot Detected

Diazepam Diazepam Not DetectedNot Detected

Nordiazepam Nordiazepam Not DetectedNot Detected

77--Aminoclonazepam Aminoclonazepam Not DetectedNot Detected

77--Aminoflunitrazepam Aminoflunitrazepam Not DetectedNot Detected

77--Aminonitrazepam Aminonitrazepam Not DetectedNot Detected

Alpha OHAlpha OH--Alprazolam Alprazolam 851 ug/L851 ug/L

Creatinine Creatinine 4.5 mmol/L4.5 mmol/L

Mass spectroscopy confirms the positive benzodiazepine screen Mass spectroscopy confirms the positive benzodiazepine screen

in this urine and indicates a pattern consistent with thein this urine and indicates a pattern consistent with the

ingestion of alprazolam as reported by the subject. Use of ingestion of alprazolam as reported by the subject. Use of

alprazolam is legitimate if prescribed. alprazolam is legitimate if prescribed. Dr Julia ChangDr Julia Chang

MS ASSAY MS ASSAY -- URINE OPIATE CONFIRMATIONURINE OPIATE CONFIRMATION

Codeine Morphine U.Creat Codeine Morphine U.Creat Cod/Creat Mor/Creat Cod/Creat Mor/Creat

(ug/L) (ug/L) (ug/L) (ug/L) (mmol/L) Ratio Ratio(mmol/L) Ratio Ratio

449 < 50 449 < 50 4.5 100 < 114.5 100 < 11

Assayed to AS/NZS 4308:2008 requirements.Assayed to AS/NZS 4308:2008 requirements.

The cutoff level for both Codeine and Morphine is 300ug/L.The cutoff level for both Codeine and Morphine is 300ug/L.

MS confirms the initial finding of Codeine at a level above theMS confirms the initial finding of Codeine at a level above the

Standards Australia threshold for reporting results as"positive"Standards Australia threshold for reporting results as"positive"..

MS confirms the opiate finding, the pattern is that MS confirms the opiate finding, the pattern is that of codeine ingestion in the 2 to 3 days prior to test.of codeine ingestion in the 2 to 3 days prior to test.There is no suggestion of illicit opiate use.There is no suggestion of illicit opiate use.

*** Updated Report ***** 1/4/2011*** Updated Report ***** 1/4/2011

Unfortunately as the MS confirmation has already Unfortunately as the MS confirmation has already

been performed and reported, it is not possible to been performed and reported, it is not possible to

cancel it.cancel it.

However I note that there has been a suggestion of However I note that there has been a suggestion of

the findings having originated from ingestion of the findings having originated from ingestion of

culinary poppy seed. We do note "epidemics" of culinary poppy seed. We do note "epidemics" of

positive drugs screens arising from this source positive drugs screens arising from this source

but the codeine/morphine pattern doesn't supportbut the codeine/morphine pattern doesn't support

this.this.

Subject questioned the finding as she denied Subject questioned the finding as she denied ingestion of any codeine containing medications and ingestion of any codeine containing medications and stated that the finding was related to ingestion of stated that the finding was related to ingestion of poppy seed. poppy seed.

Laboratory received several phone calls from the Laboratory received several phone calls from the subject, psychiatristsubject, psychiatrist’’s receptionist, subjects receptionist, subject’’s s friends, exfriends, ex--spouse, psychiatrist etc. with regards spouse, psychiatrist etc. with regards to the MS opiate findingsto the MS opiate findings

Laboratory offered to test the poppy seeds to Laboratory offered to test the poppy seeds to determine if the seed specimen contains determine if the seed specimen contains predominantly codeine predominantly codeine

DRUG SCREEN 18/04/11DRUG SCREEN 18/04/11Performed on: Foodstuff (seed mixes)Performed on: Foodstuff (seed mixes)

Drugs that were detected by thin layer chromatography Drugs that were detected by thin layer chromatography

screen:screen:

None detectedNone detected

Drugs that were detected by immunoassay only:Drugs that were detected by immunoassay only:

OpiatesOpiates

Inspection of the foodstuff received reveals theInspection of the foodstuff received reveals thepresence of poppy seeds. presence of poppy seeds. MS analysis on foodstuff reveals a morphine/codeine MS analysis on foodstuff reveals a morphine/codeine pattern which is consistent with that typically seenpattern which is consistent with that typically seenin poppy seeds (Morphine 796 ug/L, Codeine 105 ug/L,in poppy seeds (Morphine 796 ug/L, Codeine 105 ug/L,66--MAM negative). Dr Julia ChangMAM negative). Dr Julia Chang

Subsequent urine drug screens all negative for Subsequent urine drug screens all negative for opiatesopiates

Last urine sample for drug screen performed in Last urine sample for drug screen performed in October 2011October 2011


CNS depressantsCNS depressants

Sedation eg sleep, manage anxiety, relieve Sedation eg sleep, manage anxiety, relieve muscle spasms and to prevent seizuresmuscle spasms and to prevent seizures

More than 2000 have been synthesized and are More than 2000 have been synthesized and are relatively free of dangerous, acute, toxic relatively free of dangerous, acute, toxic overdose effectsoverdose effects

Detection TimesDetection Times

Chronic users Chronic users ––

positive test up to 6 weeks positive test up to 6 weeks

Occasional users Occasional users ––

positive test for 3positive test for 3--4 days4 days

PathwayPathway

A 45 year old female submitted a urine A 45 year old female submitted a urine sample for presample for pre--employment screening:employment screening:

MS ASSAY MS ASSAY -- URINE BENZODIAZEPINES CONFIRMATIONURINE BENZODIAZEPINES CONFIRMATIONDate 03Date 03/11/08/11/08Time Time 00:0000:00Lab No 8Lab No 8739023739023

Oxazepam Oxazepam 672 ug/L *672 ug/L *Temazepam Temazepam 76 ug/L76 ug/LDiazepam NDiazepam Not Detectedot DetectedNordiazepam Nordiazepam < 50 ug/L< 50 ug/L77--Aminoclonazepam Not DAminoclonazepam Not Detectedetected77--Aminoflunitrazepam Not DAminoflunitrazepam Not Detectedetected77--Aminonitrazepam Not DAminonitrazepam Not DetectedetectedAlpha OHAlpha OH--Alprazolam Not DetectedAlprazolam Not DetectedCreatinine Creatinine 18.6 mmol/L18.6 mmol/L

Assayed to AS/NZS 4308:2008 requirements (from 5/6/2008).Assayed to AS/NZS 4308:2008 requirements (from 5/6/2008).The cutoff level is 200 ug/L for the parent Benzodiazepines, aThe cutoff level is 200 ug/L for the parent Benzodiazepines, and 100 ug/Lnd 100 ug/Lfor the metabolites.for the metabolites.

Mass spectroscopy confirms the positive benzodiazepine screenMass spectroscopy confirms the positive benzodiazepine screen in thisin thisrelatively concentrated urine. This pattern can be seen severrelatively concentrated urine. This pattern can be seen several daysal daysafter use of diazepam if used as a once off, or conversely itafter use of diazepam if used as a once off, or conversely it may bemay beseen up to a month after the cessation of diazepam if prior tseen up to a month after the cessation of diazepam if prior to that, theo that, theuse was for a protracted period of time. Use of diazepam is luse was for a protracted period of time. Use of diazepam is legal ifegal ifprescribed.prescribed.


The The ““invisibleinvisible””

substances of abusesubstances of abuse

More distant cousins of the opiatesMore distant cousins of the opiates

Some designer sympathomimetic aminesSome designer sympathomimetic amines

Some benzodiazepinesSome benzodiazepines

--hydroxybutyratehydroxybutyrate

KetamineKetamine

Psilocybin and other plant hallucinogensPsilocybin and other plant hallucinogens

Lysergic acid diethylamideLysergic acid diethylamide

PhencyclidinePhencyclidine

and othersand others

ConclusionConclusion

Interpretation is often not intuitiveInterpretation is often not intuitive

Consequences of wrong interpretation Consequences of wrong interpretation can be catastrophiccan be catastrophic

Use laboratory resourcesUse laboratory resources

ToxicologyCopyright © 2008 The Royal College of Psychiatrists

ASHTON, C. H. Br J Psychiatry 2001;178:101-106

Fig. 1 Chemical structure of main cannabinoids in Cannabis sativa.

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drugs of abuse testing dr julia chang - la office · drugs of abuse testing dr julia chang. dr ......

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