The 5 most common questions

to the Toxicology Laboratory

Helen Martin
helen.martin2@sa.gov.au

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 Questions
• For how long can X be detected?
• What is the source of the morphine?
– Could it be poppy seeds?
• Has cannabis use truly ceased?
– Could passive exposure be the culprit?
• What has caused the ATS result?
– Cross-reactivity
• Source of the positive benzo

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 Drug Detection Windows
• Typically 4-6 half-lives for clearance
• Most drugs have half-lives of hours
– Most drugs cleared within 2-4 days
• ATS, most opiates
– MAM only detected in urine for 12-24 hours
– Some Bz present for a week or even 4-6 weeks
– THC: single dose ~2 days, low dose casual use ~2
weeks. High dose chronic users often positive for 4-6
weeks, potentially up to 12 weeks.
• Generalizations – may not apply to a given
individual
– Influenced by dose, dose frequency, ingestion route,
fluid status, urine pH, pharmacogenomic status.

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For our patients and our population
 What is the source of the
morphine?
Codeine, morphine, heroin, poppy
seeds……?

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~10% ~90%

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Difficulties in Opiate Interpretation
• Arise because codeine and heroin both
metabolise via morphine.
• Poppy seeds also contain morphine.
• MAM is heroin specific, but has a short
half-life
• When MAM is not present interpretation
can be difficult.
– Careful evaluation of both the absolute and
relative amounts of codeine and morphine are
usually helpful.

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 Morphine Codeine Ratio
• MCR proposed as an aid to assigning
the source of morphine.
– MCR from >0.5 to >10.0 have been
proposed as supporting heroin use.
• High MCR favours SP, lower favours SN
– Some authors include aditional
requirements:
• codeine >LOQ
• Morphine >2000 ug/L

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Case: Opiates. 35 yo M
No medication declared
Immunoassay screen “detected” for
Opiates 2678 ug/L
GC/MS confirmation
Codeine 33553 ug/L
Morphine 3853 ug/L
Interpretation
The opiate levels detected are consistent
with codeine as the source of the morphine

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 Case Opiates. 52 yo M
Nil medication declared
Immunoassay screen “detected” for
opiates 2391 ug/L (and THC and ATS)
GC/MS (opiates) Morphine 4033 ug/L
Codeine 310 ug/L
Interpretation
Note it is very unlikely that the morphine
has been derived from codeine alone.
Recent heroin use is likely.
(morphine + codeine also possible)
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Case: Opiates. 35 yo F
Stated medication: Valium
Immunoassay screen “detected” for
Bz, Bup, Op, MAM, ATS, THC
GC/MS confirmation positive for
MAM 475 ug/L
Morphine 27354 ug/L
Codeine 3595 ug/L
Interpretation. C/W recent heroin
use.
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Case: Opiates. 27 yo F
Stated medication: Methadone
Immunoassay screen “detected” for
Op, MAM
GC/MS confirmation positive for
MAM 18 ug/L
Morphine 2566 ug/L
Codeine 17223 ug/L
Interpretation. C/W recent heroin
use.
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Case: Opiates. 41 yo F
Clinical notes: On methadone

Immunoassay screen: “detected”

for Opiates 2619 ug/L Medical test. GC/MS

MAM 30 ug/L
not performed.

Md 424 ug/L
Interpretation
Methadone consistent with medication.
MAM detected by immunoassay screen.
Recent heroin use is likely.

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Case: Screen not confirmed
On-site screen “non-negative” for Op
Lab immunoassay opiates detected 886 ug/L
GC/MS (Morphine 298 ug/L)
(Codeine 207 ug/L)

Report “not detected” for opiates

NB this interpretation applies to AS/NZS 4308:2008

samples only. A medical sample with these results
would record morphine, codeine. The origin of the
morphine can not be determined at these levels.

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 Poppy seed defence
• Opiate content of poppy seeds
depends on seed origin and method
of preparation
– Morphine ranges from 0.1 – 294 ug/g
• Higher the morphine the less likely
poppy seeds can be the source.
• US implemented a 2000 ug/L opiate
cut-off to avoid the poppy seeds
defence

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Author Poppy seed g Morphine Mean Morphine peak
dose mg Morphine range
peak ug/L ug/L
Fritschi 33 (cooked) 2.5 1200 700-1900
150 30 18000
(ground,raw)
Hayes 40 2,635

El Sohly 15 2.5 2,010

Thevis ~4.5 4400 3530-5760

~6.2 7273 5880-10040

Smith 2 x 45 (8hrs 2 x 15.7 5239 2413-7522
apart, raw)

Samano 15 (cooked) 697 258-1356

15 (raw) 1743 399-4213

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 Case Opiates. 30 yo M
Declared medication. Valium, suboxone,
nurofen plus
Immunoassay screen “detected” for
opiates 1798 ug/L (and bup and Bz)
GC/MS Morphine 718 ug/L
(Codeine 187 ug/L)

Interpretation. Very unlikely that the morphine

has been derived from codeine alone. At the low
levels of morphine detected, heroin or poppy seeds
are both possible.
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For our patients and our population
 THC elimination
• One-off use eliminated within a few days
• Low level, occasional use ~ 1 week
• High level chronic use harder to predict
– likely a majority will be negative within 1
month. A small number may take 3 months.
• Factors affecting THC elimination in the
high level, chronic user
– Starting concentration.
– Dose and frequency of dose
– Time of continued use
– Fat stores Age at first use

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Evaluation of true THC abstinence

• Must look at the THC/creatinine ratio not

the concentration level.
• Ideally the ratio will continuously fall in
consecutive samples. Typically does for a
low level user.
• High level users have confounders like
THC stored in fat tissue.
• Compare c-THC/creat ratio in successive
samples – the ratio of the ratios (U)

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 Models for detection of new
cannabis use
• 4 days half-life
• Huestis: U = >0.5
– Applies to casual users
• Smith
– Realistic
– Conservative
• Manno: U = >1.5
– Applies to high dose chronic users

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THC/creatinine ratios on samples from a 20
y.o pregnant women

Same data, log plot

Elimination half-life
19 days

Commencing at week 31/40.

Subject claimed THC use ceased after the first positive result

Westin et al Journal Analytical Toxicology 2009

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For our patients and our population
 Case THC. 17 yo F
Collection THC Urine THC/creat Ratio of the
date (GC/MS) Creatinine ratio Ratios
ug/L mmol/L (U)

15/08 3011 16.6 181.4

20/08 735 21.1 34.8 0.19
27/08 57 3.6 15.8 0.45
01/09 365 3.4 107.3 6.8

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 Case THC. 19 yo M
Collection GC/MS c-THC Creat THC/Crt
date ug/L conc ratio
U
mmol/L ug/mmol

03/10 71 1.0 71 5.73

10/10 405 9.2 44 0.62

Declared use

17/10 46 0.9 51 1.16

Declared no use

28/10 193 12.6 15.3 0.30

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 Case 6 60 y.o. male
20 year heavy chronic THC use
HCV and hepatoma

In hospital for liver transplant work up

Routine urine drug screen THC
detected
Claims last THC use 3 months ago
? Truly abstinent.

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 GC/MS results
Date Carboxy Creatinine THC/Cr
collected THC (µg/L) (mmol/L) ratio
17/01/2013 20 17.2 1.2

24/01/2013 6 6.9 0.9

Ratio of the Ratio’s = 0.75

Applying the Manno model for heavy chronic users in the terminal elimination phase
this ratio is consistent with true abstinence

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 Passive THC
• Experiments have shown that THC can be
detected following passive exposure to
THC smoke, but only in extreme
circumstances and for only a few hours
post exposure.
– Cone et al JAT 2015

• Cut-offs set in the AS/NZS 4308:2008

standard for confirmation are set at levels
to minimize the possibility of false positive
detection of passive smoking.

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For our patients and our population
 The methamphetamine
result is due to…..
• Other medications
– Pseudoephedrine
– Ranitidine
– Blood pressure medications
• My hormones
• Nail polish salon chemicals

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 Amphetamine Type Substances
• Calibrated with amphetamine
– AS/NZS 4308:2008 cut-off 300 ug/L
• Positive results (reactivity compared with
amphetamine)
– Methamphetamine (300 ug/L)
– MBDB (300 ug/L)
– MDA (300 ug/L)
– MDMA (200 ug/L) Ranitidine negative at 250,000 ug/L
– PMMA (300 ug/L) Methylphenidate negative at 300,000 ug/L
– PMA (1,260 ug/L)
– Phentermine (9,000 ug/L)
– Pseudoephedrine (30,000 ug/L)
– Ephedrine (60,000 ug/L)
– Buproprion (5,400 ug/L)

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 ATS GC/MS experience
• ~96% of GC/MS confirmations for ATS are
positive for methamphetamine
• Methamphetamine is only positive due to
methamphetamine (within last 3-4 days)
• High levels of amphetamine only, c.w.
dexamphetamine therapy
• Low levels of amphetamine only can also
be seen in the terminal elimination of
methamphetamine
• Occasionally see phentermine
• ? Other “false positive” ATS
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Case ATS. 30 yo F
Declared medications: Duramine, sudafed
Immunoassay screen “detected” for ATS
GC/MS Phentermine 16105 ug/L
Methamphetamine 8729 ug/L
Amphetamine 3064 ug/L.

Interpretation. Phentermine c/w declared

medication duramine. Note also recent
methamphetamine use.

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 Case ATS. 25 yo M
No declared medication.
Immunoassay screen “detected” for
ATS. Creatinine 0.7 mmol/L
GS/MS Methamphetamine 789 ug/L
(Amphetamine 90 ug/L)
Creatinine <1.8 mmol/L may indicate
a dilute sample.
Positive result still true.

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 Benzodiazepines
• Commonly prescribed
– ~6.5 million scripts Australia wide 2014
• 72% for Temazepam or Diazepam
• Commonly abused
– Clinical questions
• Compliance with prescribed drug
• Taking a not prescribed Bz: ? alprazolam

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 Image:Pharma GKB

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 72% prescribed Bz
Diazepm or Temazepam.
Further 16% Oxazepam

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• Melb path data for 35 declared
diazepam users: O>T>N
– O:T ratio 1.1-5.7
– T:N ratio 1.0-4.6
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Benzodiazepines detected by GC/MS (ug/L)
Oxaz Temaz Nordiaz Alpraz Inferred Bz use

2928 1898 843 Diazepam

2937 155 Oxazapam and
Alprazolam
32318 Oxazepam
51177 2154 2333 Diazepam and
Oxazepam
811 12766 Temazepam
387 ?
3775 376 88 Diazepam and
Oxazepam

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Questions?

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