1. Drug Testing: A Critical Clinical Tool
Kirk Moberg, MD, PhD, FASAM
Executive Medical Director, Illinois Institute for Addiction Recovery
Clinical Professor of Internal Medicine and Psychiatry & Behavioral Medicine
University of Illinois College of Medicine
Illinois Alcohol and other Drug Abuse Professional Certification, Inc.
Itasca, IL
March 22, 2017

3. Unfortunately
Drug test results are often misinterpreted

4. Drug Tests do not detect
Impairment
Addiction
Diversion
Physiologic Dependence

5. Pearl #1 Drug Tests detect

6. Pearl #1 Drug Tests detect
Recent Use

7. Pearl #2 You only get what you test for…

8. Goals of testing Discover if compounds are present that should not be.
Confirm that compounds are present that should be.

9. Pearl #3 Timing is everything
Intoxication
Minutes to hours
Impairment
Under Influence
Blood
Minutes to days
Oral fluid
Urine
Hours to days
Sweat
Weeks
Hair
Days to years

10. Pearl #4 Know your source

11. The question is: is the concentration in the body fluid in equilibrium with blood?

12. Oral fluids Pros Easy to collect Difficult to adulterate
Correlation between concentration and impairment
Detects recent use
Cons
Saliva production rate variable
Oral and smoked drugs contaminate saliva
Narrow window of detection

13. Sweat Pros Noninvasive Relatively tamper proof
Long term monitoring (1-2 weeks)
Criminal justice system
Cons
Variable rate in sweat production
Total sweat production not known
Accidental removal
Possible environmental contamination
Intersubject variability

14. Sweat can be used to detect
Ethanol
Nicotine/Cotinine
Morphine
Amphetamine
Methamphetamine
PCP
Methadone
Cocaine

15. Hair Long time window Easy to collect Second collection capability
Noninvasive
May not detect recent use
Environmental contamination
New science with few controlled studies

16. A drug test has two components

17. Immunoassay screens Antigen/Antibody reactions
If concentration of drug is above the cut off then the test is positive.

18. Pearl #5 Don’t Jump the Gun The Problem of False Positives and Negatives
Class specific false positives
Forensic false positives
False Negatives

19. Same class Opiates Morphine Codeine 6-monoacetyl-morphine Hydrocodone
Oxycodone

20. Same class Amphetamines (not comprehensive) Amphetamine
Methamphetamine
3,4-Methylenedioxyamphetamine (MDA)
3,4-methylenedioxymethamphetamine (MDMA)
3,4-methylenedioxyethylamphetamine (MDEA)
Selegiline
Bupropion

21. Forensic false positive
Amphetamine/Methamphetamine
Chloroquine
Labetalol, propanolol
Mexiletine,
Ranitidine
Trazodone
LSD
Amitriptyline
Verapamil
Chlorpromazine, thioridazine
Doxepin
Fluoxetine, sertraline
Haloperidol
Metoclopramide

22. Forensic false positives
Barbiturates
Phenytoin
Benzodiazepines
Oxaprozin (Daypro®)
Opiates
Fluoroquinolones (ofloxacin, levofloxacin)
Cannabinoids
Pantoprazole (Protonix®)
Efavirenz (Sustiva®) HIV medication
Phencyclidine
Venlafaxine (Effexor®)
Dextromethorphan

23. Immunoassay screens Antigen: antibody reactions
Point of care
Competitive type
Sandwich type
Reference labs
Label
Analyte
Antibody

24. Point of Care Testing
Competitive type: positive test will show one line
Conjugate: colored particles labelled with target analyte
Test line: antibodies to target analyte; unlabelled
analyte will bind to test lineno color
Control line: antibody to compound in matrix
Urine flow
Salt/sugar matrix

25. Sandwich method

26. Confirmation
Discussion
Further analysis

27. Further analysis: GC/MS or LC/MS
GC—separation
MS—identification
Cannabis metabolites

28. Output is quantitative
Dependent upon
Exposure time
Dose
Frequency and pattern of use
Not an indication of compliance

29. Pearl #6—Cutoffs (ng/mL)
Opiates—2000
Morphine—2000
Codeine—2000
6-acetylmorphine—10
6-AM—10
Amphetamines—500
Methamphetamine—250 (with amphetamine—100)
Amphetamine, MDMA, MDA, MDEA—250
Phencyclidine—25
PCP—25
Benzoylecognine—150
BE—100
THC—50
THC—15

30. Cut-offs

31. Department of Transportation
Opiates
Morphine
Codeine
6-monoacetyl-morphine
Amphetamines
Amphetamine
Methamphetamine
MDA
MDMA
MDEA
Cocaine
Marijuana
Phencyclidine

32. Opioids
Opioid cutoff = 2000 ng/mL

33. Testing issues Restriction of testing Burden of proof
Morphine
Codeine
Heroin metabolite
Burden of proof
Borne by the MRO
Cross reactivity and metabolites

34. CODEINE
HEROIN
NOR-CODEINE
non-analgesic
MONO-ACETYL MORPHINE
CODEINE-6-GLUCURONIDE
analgesic
MORPHINE-6-GLUCORONIDE
Analgesic (6-10%)
NOR-MORPHINE
non-analgesic
MORPHINE-3-GLUCORONIDE
non-analgesic
Seizures (60%)
MORPHINE

35. Unique Burden of Proof: borne by MRO unless…
15,000 ng/mL morphine
6-monoacetyl morphine
Clinical evidence of opiate abuse

36. 4 reasons for positive urines (morphine/codeine)
Ingestion of poppy seeds (?)
Use of codeine containing products
Use of morphine containing products
Use of heroin
Hamantashen
Mohn = poppy seed
Tash = pocket

37. Yes, with regards to poppy seeds
Types of poppy seeds
How prepared

38. There are bagels… and there are bagels
IF…
Bagel has 1-2 tsp poppy seeds
12 bagels = 10 mg morphine

39. Desserts
3-4 slices = 10 mg morphine

40. What to do?
Thebaine:
poppy seed—yes
heroin—no

41. A “typical” opiate screen
Morphine
Codeine
6-monoacetyl-morphine
Hydrocodone
Oxycodone

42. Pearl #7 Know your lab

43. Stimulants

44. Cocaine
COCAINE
(METHYLBENZOYLECGONINE)
BENZOYLECGONINE

45. Other “caines” Lidocaine, Benzocaine, Mepivacaine
I just went to the dentist!

46. Cocaine in Tea Illegal in U.S. unless decocainized
Yerba mate (Uruguay & Argentina) vs. Coca mate (Argentina, Bolivia, Peru)

47. b-phenylethylamines 3,4 methylenedioxyamphetamine (MDA) amphetamine
3,4 methylenedioxymethamphetamine (MDMA)
methamphetamine
3,4 methylenedioxyethylamphetamine (MDEA)
b-phenylethylamines
3,4 methylenedioxyphenyl-2-butanamine (MBDB)

48. Issues in testing
Metabolism of amphetamines
Sterioisomers

49. Amphetamine testing Metabolism
Metabolism and elimination
Orally: 30-54% methamphetamine; 10-23% amphetamine
IV: 45% methamphetamine; 7% amphetamine

50. Amphetamine Testing Chirality

51. So what?!

52. Chirality
Screening test
Confirmatory test

53. Methylenedioxymethamphetamine MDMA

54. Synthetic cathinones (bath salts)
Ephedrone
Mephedrone
Methylone
MDPV
Valente et al., 2013

55. Methcathinone (ephedrone) metabolism
norephedrine
cathine
cathinone
methcathinone
ephedrine
both methcathinone and ephedrine will cross react with
methamphetamine on immunoassays

56. Cannabis
11 hydroxy THC

57. Issues Dronabinol (Marinol®) Creatinine correction Passive inhalation
Hemp oil, hempseed oil, hemp seed
Marijuana used for medical conditions
Synthetic cannabinoids

58. Dronabinol

59. Creatinine correction
Cannabis level at entry
193
Cannabis level one week later
234

60. Creatinine correction
Urine Creatinine concentration at entry: 193
Urine Creatinine concentration one week later: 288

61. Formula Cannabis at entry x normalized Cr/Cr at entry
= normalized cannabis
193 x 100/193 = 100
Cannabis one week later x normalized Cr/Cr one wk later
234 x 100/288 = 81

62. Pearl #8 Passive exposure
6 volunteers, 8x8x7 ft enclosed room exposed to 200 mg freebase cocaine vapor—all negative urines
3 marijuana non-smokers exposed to 8 smokers (32 joints) in a 10x10x8 enclosed room—all negative urines

63. There’s more…common theme
Cut off is 20 ng/mL by immunoassay
DOT cutoff is 50 ng/mL

64. Legal status

65. Hemp oil and hemp seed

66. Sedatives Issues in Testing
Long half-lives

67. Detectability in Urine Sedatives
Barbiturates
Ultra short acting (thiopental)
24 hours
Short acting (secobarbital, butalbital)
Intermediate acting (pentobarbital)
48-72 hours
Long-acting (phenobarbital)
16 days or more
Benzodiazepines
Short acting (triazolam, alprazolam)
Intermediate acting (temazepam, chlordiazepoxide)
40-80 hours
Long-acting (diazepam)
7 days or more

68. Benzodiazepine metabolism
Nordiazepam = hours

69. Alcohol testing

71. Ethyl gluconoride (EtG)/ Ethyl sulfate (EtS)

72. Metabolic pathways

75. Sample contamination
In vivo
In vitro

76. Pearl #9 People do the darndest things

77. Case: Henry
This is a 39 year old man with history of chronic pain to the right hip s/p MVA in He has had a THR that became infected and required 2 revisions.
He reports pain management with OxyContin 40mg BID “down from 80” and occasional diazepam.
On addiction interview, he says “I was in the service. I have never used drugs!” 77

78. Case: Henry, UDT 78

79. Case: Henry, UDT
He states,
“Your lab screwed up. It’s not my urine. I’ll do another test right now.” 79

80. Case: Henry, UDT 80

81. Examples of Metabolism of Opioids
Codeine
Morphine
6-MAM*
Heroin
t½=25-30 min
t½=3-5 min
Hydrocodone
Hydromorphone
Oxycodone
Oxymorphone
Not comprehensive pathways, but may explain presence of apparently unprescribed drugs
*6-MAM=6-monoacetylmorphine
Gourlay DL, et al. Urine Drug Testing in Clinical Practice. The Art & Science of Patient Care. Ed

82. Benzodiazepine metabolism

83. Case: Henry, UDT
“ OK, doc. I did use cocaine twice Once on Jan 1 and once on Feb 1. No other times.” 83

84. Hmm…
What’s going on?
What do you recommend?

85. Drug Test Quiz

86. Drug Screen Results Opioids present Fentanyl Morphine Naltrexone
Codeine
Methadone
Buprenorphine
Hydrocodone
Meperidine
Oxycodone
6-monoacetyl-morphine
Propoxyphene

87. Drug Screen Results Opioids present Fentanyl Morphine Naltrexone
Codeine
Methadone
Buprenorphine
Hydrocodone
Meperidine
Oxycodone
6-monoacetyl-morphine
Propoxyphene

88. Drug Test results
6-monoacetyl-morphine and morphine present

89. Drug Test results
6-monoacetyl-morphine and morphine present
Heroin

90. Drug test results
Morphine and quinine present

91. Drug test results
Morphine and quinine present

92. Drug test results
Morphine and quinine present

93. Drug Test results
Large amounts of hydrocodone and oxycodone

94. Drug Test results
Large amounts of hydrocodone and oxycodone

95. Drug Test results
Less than 10% hydrocodone in a patient taking codeine

96. Drug Test results less than 10% hydrocodone in a patient taking codeine

97. Drug Test results less than 10% hydrocodone in a patient taking codeine
Morphine
6-MAM*
Heroin
t½=25-30 min
t½=3-5 min
Hydrocodone
Hydromorphone
Oxycodone
Oxymorphone
*6-MAM=6-monoacetylmorphine

98. Drug Test results
Buprenorphine present

99. Drug Test results
Buprenorphine present
and nor-buprenorphine absent

100. Drug Test results
Buprenorphine present
and nor-buprenorphine absent

101. Drug Test results
Your patient’s urine drug test shows benzoylecgonine is present. She says
She received the medicine in the Emergency Department. Could this be true?

102. Drug Test results
Your patient’s urine drug test shows benozylecgonine is present. She says
she received the medicine in the Emergency Department. Could this be true?
The American Academy of Otolaryngology-Head and Neck Surgery considers cocaine to be a valuable anesthetic and vasoconstricting agent when used as part of the treatment of a patient by a physician. No other single drug combines the anesthetic and vasoconstricting properties of cocaine.
Position Statement—Medical Use of Cocaine

103. Drug Screen results
Methamphetamine present in a patient treated for depression

104. Drug Screen results
Methamphetamine present in a patient treated for depression

105. Drug Screen results A patient with Parkinson’s Disease has a UDS
which shows methamphetamine present

106. Drug Screen results A patient with Parkinson’s Disease has a UDS
which shows methamphetamine present

107. Drug Test results True or False
Synthetic cannabinoids will test positive for cannabis on
the screen but not on the confirmation

108. Drug Test results True or False
Synthetic cannabinoids will test positive for cannabis on
the screen but not on the confirmation

109. It is impossible to test for synthetic cannabinoids at this time
Drug Test results
True or False
It is impossible to test for synthetic cannabinoids at this time

110. It is impossible to test for synthetic cannabinoids at this time
Drug Test results
True or False
It is impossible to test for synthetic cannabinoids at this time

111. What assists in the drug test interpretation of urine in which cannabis and ethyl glucoronide are present?

112. What assists in the drug test interpretation of urine in which cannabis and ethyl glucoronide are present?
Cut-offs

113. Drug Test results
A physician is a patient in the Illinois Professional Health Program.
He produces an observed urine sample. His urine shows the presence
of no substances tested. However, epithelial cells are present in the urine.

114. Drug Test results
A physician is a patient in the Illinois Professional Health Program.
He produces an observed urine sample. His urine shows the presence
of no substances tested. However, epithelial cells are present in the urine.

115. Additional info Microsomal enzyme system
Uridine diphosphate-glucurolyosyltransferase
Sulfotransferase
Fermentation issue
Degradation issue
5:1 ratio
Cut offs
EtG 500 ng/mL
EtS 100 ng/mL

116. Some final generalizations
Benzodiazepines can be easier to detect with current technology.
The so-called “Z drugs” (zolpidem, etc.) are now detectable by new technology but only if requested.
Some semi-synthetic (buprenorphine) and all synthetic (methadone, fentanyl) opioids will not cross react on a general opioid screen.
Newer synthetics such as synthetic cannabinoids and synthetic cathinones may not show up on some panels and others will not show up on any.

117. Final Clinical Pearl
The drug(s) most easily abused are the ones legitimately present in the urine.

118. Most importantly…
A drug test is an ingredient, the interpreter is the chef.

120. Detectability in Urine Stimulants
Amphetamine
2-3 days
Methamphetamine
48 hours
MDMA
30-48 hours
Cocaine
6-8 hours
Benzoylecgonine (cocaine metabolite)

121. Detectability in Urine Sedatives
Barbiturates
Ultra short acting (thiopental)
24 hours
Short acting (secobarbital, butalbital)
Intermediate acting (pentobarbital)
48-72 hours
Long-acting (phenobarbital)
16 days or more
Benzodiazepines
Short acting (triazolam, alprazolam)
Intermediate acting (temazepam, chlordiazepoxide)
40-80 hours
Long-acting (diazepam)
7 days or more

122. Detectability in Urine Opioids
Methadone (maintenance dosing)
7-9 days
Codeine/morphine
24 hours
6-monoacetyl morphine
2-4 hours
Morphine glucuronides
48 hours
Codeine glucuronides
3 days
Propoxyphene/Norpropoxyphene
6-48 hours
Dihydrocodeine
Buprenorphine
48-56 hours
Buprenorphine conjugates
7 days

123. Detectability in Urine Cannabinoids
Single Use
3 days
Moderate Use
4 days
Heavy Use (daily)
10 days
Chronic Heavy Use
Up to 36 days

124. Detectability in Urine Others
Methaqualone
7 days or more
PCP
8 days
LSD
24 hours
Nicotine
12 hours
Cotinine (Nicotine metabolite)
2-3 days