Interpretation Of Urine Drug Testing Results For Pain … · 2019. 3. 31. · Structured Method For Proper Drug Testing Interpretation Example: “Mr. Smith was found to be positive

Interpretation Of Urine

Drug Testing Results For

Pain Management

Alec Saitman, PhD, DABCC (CC, TC)

Director of Special Chemistry and Toxicology

Providence Regional Laboratories

The Intent Of The Session

Provide an introductory overview of structured drug

interpretation

Didactic lecture

Discuss typical and atypical case examples

And how to interpret them

Panel member discussion in real time

Requirements Before Any

Drug Interpretation

Technical knowledge of drug screening methodologies

If applicable

Screening cutoffs

Known interferences

Technical knowledge of confirmation methodologies

What parent drugs and metabolites are tested

Whether drugs are hydrolyzed or not prior to testing


Drug Interpretation

All chromatographic data is:

Thoroughly reviewed by trained staff

Free of any chromatographic interferents

An updated medication list is available

Knowledge of prescribed medications

Parent drugs contained within them

At what dose

At what frequency


Drug Interpretation

Ability to interpret use of illicit/non-prescribed drugs

Heroin

Methamphetamine/Amphetamine

Cocaine

Barbiturates

THC

PCP

Kratom

Pain management populations at high risk for illicit drug abuse

Drug testing for illicit use is typical


Drug Interpretation

Thorough understanding of metabolism patterns of

drugs tested

Drug

Drug

Metabolite

Metabolite

Structured Method For Proper

Drug Testing Interpretation

Step 1

Identify all expected results

Using medication list

Knowledge of parent drugs and metabolites tested

Example: Mr. Smith prescribed methadone only

Possible expected results are

Methadone and EDDP (metabolite)

Methadone EDDP



Step 2

Identify all observed results

Using final confirmation data for particular drug collection

Example: Mr. Smith is positive for

Methadone

EDDP

Oxycodone

Noroxycodone

Oxymorphone



Step 3

Identify whether the patient is

Compliant with medications prescribed

Not Compliant with medication prescribed.

Example: “Mr. Smith is not compliant with medications

prescribed.”



Step 4

Provide explanation/interpretation of decision

Explain any and all discrepancies observed for this testing

Note all parent drugs and metabolites which should have existed but

do not

Note all parent drugs and metabolites which should not have existed

but do

Be concise

Recommend using templates to maintain consistency



Example: “Mr. Smith was found to be positive for methadone and

its metabolite EDDP indicating the use of a drug containing

methadone. Mr. Smith was also found to be positive for oxycodone

along with its metabolites noroxycodone and oxymorphone. This

pattern indicates the use of a drug containing oxycodone.

Although the presence of methadone and EDDP is expected, the

presence of oxycodone and its metabolites is inconsistent with

the medications prescribed”

Many Times, Unexpected Drug

Results Exist That Can

Complicate Interpretation

What are these circumstances?

1. Pharmaceutical Impurities

2. Metabolism Abnormalities

3. Diversion Tactics

4. Drug Detection Windows

5. False Negative Drug Screening

6. False Positive Drug Screening

Pharmaceutical Impurities

May Be Present

Commercial Active

Pharmaceutical

Ingredient (API)

Process

Impurities

Allowable

Limit (%)

Typical

Observed (%)

Morphine Codeine 0.5 0.01-0.05

Codeine Morphine 0.15 0.01-0.1

Hydrocodone Codeine 0.15 0-0.1

HydromorphoneMorphine

Hydrocodone

0.15

0.1

0-0.025

0-0.025

Oxycodone Hydrocodone 1 0.02-0.12

OxymorphoneHydrocodone

Oxycodone

0.15

0.5

0.03-0.1

0.05-0.4


May Be Present

Very common when main drug is found in high

concentrations (>5,000 ng/mL)

Allowable pharmaceutical limits can guide interpreters

as to whether there is an impurity or co-use


May Be Present

Example: Sample contained 7,983 ng/mL Oxycodone

But also contained 23 ng/mL Hydrocodone

0.29% < 1.0 % allowable impurity limit

Likely pharmaceutical impurity and not co-use


May Be Present

Example: Sample contained 8,247 ng/mL Oxycodone

But also contained 169 ng/mL hydrocodone

2.0 % >1.0% allowable impurity limit

Likely co-use and not pharmaceutical impurity







Impact On CYP450 Deficiencies

And Co-Use Of Drug Inhibitors.

Up to 80% of drugs are metabolized by CYP enzymes

Drug

Drug

Metabolite

Metabolite

CYPCYP

CYP



CYP2C19

8%

CYP1A2

11%

CYP2C8/9

16%CYP2D6

19%

CYP3A4/5

36%

CYP2E1

4%

CYP2B6

3% CYP2A6

3%



Germline Variants

Slow Metabolizers

Intermediate Metabolizers

Rapid Metabolizers (Normal Metabolizers)

Ultra-rapid Metabolizers

Inhibitors and Inducers

Co-use of pharmaceutical drugs

Consumption of Food-Based Biologicals

Ex. Grapefruit Juice can inhibit CYP3A4 metabolism

Drug Metabolite



CYP2D6CYP3A4

Hydrocodone

1,549 ng/mL

Norhydrocodone

1,939 ng/mL

Hydromorphone

34 ng/mL



CYP2D6CYP3A4

Hydrocodone

1,549 ng/mL

Norhydrocodone

1,939 ng/mL

Hydromorphone

<10 ng/mL



CYP2D6CYP3A4

* In my lab, 38% of patients with both hydrocodone and

norhydrocodone >500 ng/mL did not have a hydromorphone

>10 ng/mL.

HydrocodoneNorhydrocodone Hydromorphone







Diversion Tactics And What To

Look For

Diversion is not taking a prescribed drug when one

should be

Selling drugs

Hoarding drugs

Forgetting to take drugs

Masking diversion by adding drug directly to urine


Look For

Example 1

Oxycodone 2,934 ng/mL

Noroxycodone 3,145 ng/mL

Oxymorphone 157 ng/mL

Example 2


Noroxycodone <10 ng/mL

Oxymorphone <10 ng/mL

How do we know this is not a error or inhibition in metabolism?


Look For

Example 1


Noroxycodone 3,145 ng/mL

Oxymorphone 157 ng/mL

Example 2


Noroxycodone <10 ng/mL

Oxymorphone <10 ng/mL

Look at past drug results. Did they have typical drug metabolism patterns?


Look For

Example 1

Buprenorphine 835 ng/mL

Norbuprenorphine 674 ng/mL

Naloxone <100 ng/mL

Is this diversion?

Example 2

Buprenorphine 2,835 ng/mL

Norbuprenorphine 16 ng/mL

Naloxone 3601 ng/mL

Is this diversion?







Detection Windows

Detection windows

“My patient claims they took XX tablets of XX drug XX days

ago but the sample is screened and/or confirmed

negative. Is that possible?”

“My patient claims they haven’t used XX drug of since XX

days ago but the sample is screened and/or confirmed

positive. Is that possible?”

Drug Metabolite(s)Detection Window

(Days)

HydrocodoneNorhydrocodone

Hydromorphone1-4

Hydromorphone N/A 1-4

CodeineMorphine

Hydrocodone1-4

Morphine Hydromophone 1-4

OxycodoneNoroxycodone

Oxymorphone1-4

Oxymorphone N/A 1-4

Buprenorphine Norbuprenorphine 1-6

Fentanyl Norfentanyl 1-4

Methadone EDDP 1-5

Detection Windows

Know your common detection windows for the drugs you

analyze

Know that detection windows have many variables

Use caution with providing strong-worded interpretation

on detection windows

Ex. “Based on the presence of the metabolite for

oxycodone, the patient has likely ingested a drug

containing oxycodone in the last 1-4 days”







False Negative Drug

Screening May Have Occurred

Many drug screening algorithms only reflex presumptive

positive results

False negative results common for particular

benzodiazepines prescribed

Clonazepam and sometimes Lorazepam

Why Do Some Screens Not

Pick Up Benzodiazepines?

Oxazepam Clonazepam 7-amino

clonazepam

Many screening

antibodies are

raised against




clonazepam

This prescribed

benzodiazepine

extensively

metabolizes to




clonazepam

This metabolite which is

structurally too dissimilar

to oxazepam to be

detected reliably







False Positive Drug Screening

May Have Occurred

“My patient screened positive for methamphetamine

but confirmed negative. What caused the false

positive?”

False Positive Drug Screening

May Have Occurred

“My patient screened positive for methamphetamine

but confirmed negative. What caused the false

positive?”

Serotonin Norepinephrine

Dopamine

Other Frequently Asked

Questions From Providers

Positive because of passive exposure

“My patient claims they were in an apartment where

others were using cocaine and that is why they are

confirmed positive at 7,305 ng/mL.”

“Is this possible?”

Other Medication causing positive confirmed illicit drug

“My patient claims they took Tylenol 3 (from a friend) and

that is why they are positive for heroin metabolite at 348

ng/mL”

“Is this possible”

Moving Into Case Presentations

All further discussions are based off of real cases

Some data may have been altered for demonstration

purposes

Case Study 1Presented by: Alec Saitman PhD, DABCC (CC, TC)

Director of Toxicology and Special Chemistry

Providence Regional Laboratories, Portland, OR

Case Study 1-Background

Patient and History

35 y/o female

Persistent pain following a MVA 3 years prior

Current Medications

Percocet®

(oxycodone and acetaminophen 5/325 mg 2X daily)

Case Study 1-Results

Screened positive for oxycodone

By IA at 100 ng/mL oxycodone cut-off

Confirmed for

Oxycodone at 738 ng/mL

Noroxycodone at 984 ng/mL

Oxymorphone at 24 ng/mL

Case Study 1-Panel Discussion

Step 1: Identify all expected results

Step 2: Identify all observed results

Step 3: Identify whether the patient is



Step 4: Provide explanation/interpretation of decision

Case 1- Final Interpretation

Case Study 2Presented by: Deborah French Ph.D., DABCC (CC, TC), FAACC

Assistant Director of Chemistry and Director of Mass Spectrometry

at the University of California San Francisco Medical Center


Patient and History

71 y/o male

Depression

Hypertension

Persistent pain

Current Medications

Norco®

(hydrocodone and acetaminophen 5/325 mg 4 times daily)

Zestril®

(Lisinopril 5 mg daily)

Wellbutrin®

(bupropion 150 mg daily)


Screened positive for opiates

By IA at 300 ng/mL Opiates cut-off

Confirmed for

Hydrocodone at 76,254 ng/mL

Norhydrocodone at 84,528 ng/mL

Hydromorphone at 5,402 ng/mL


Noroxycodone at 76 ng/mL

Oxymorphone at < 10 ng/mL









Case Study 3Presented by: Deborah French Ph.D., DABCC (CC, TC), FAACC

Assistant Director of Chemistry and Director of Mass Spectrometry

at the University of California San Francisco Medical Center


Patient and History

46 y/o female

Anxiety

Persistent pain

Current Medications

Norco®

(hydrocodone and acetaminophen 10/325 mg 4 times daily)

Xanax®

(Alprazolam 1 mg daily)

Case Study 3-Results Screened positive for opiates only

By IA at 300 ng/mL opiates cut-off

Confirmed for

Hydrocodone at 70,906 ng/mL

Norhydrocodone at <10 ng/mL

Hydromorphone at <10 ng/mL


Noroxycodone at <10 ng/mL

Oxymorphone at < 10 ng/mL

Directly analyzed for

Alprazolam at <10 ng/mL

a-hydroxy alprazolam at <10 ng/mL









Case Study 4Presented by: Amadeo Pesce Ph.D. DABCC

Professor in the Department of Pathology and Laboratory Medicine, University of California, San Diego, School of Medicine

Laboratory Director Precision Diagnostics LLC, San Diego


Patient and History

55 y/o male

Depression

Persistent pain

Current Medications

Tylenol 3®

(Tylenol and acetaminophen 15/300 mg 4 times daily)

Prozac®

(Fluoxetine 40 mg daily)


Screened positive for opiates

By IA at 300 ng/mL opiates cut-off

Confirmed for

Codeine at 2,150 ng/mL

Morphine at <10 ng/mL

Hydrocodone <10 ng/mL

Norhydrocodone at 150 ng/mL

Hydromorphone at <10 ng/mL









Case Study 5Presented by: Frederick G. Strathmann, PhD, MBA, DABCC (CC, TC)

Vice President of Quality Assurance, Director of New Technology and

Innovation, and Assistant Laboratory Director, NMS Labs, Horsham, PA


Patient and History

61 y/o male

Persistent pain

In addiction treatment

Current Medications

Suboxone®

(Buprenorphine and naloxone 4/1 mg daily)


Screened negative for all drug components

Confirmed for

Buprenorphine at 142 ng/mL

Norbuprenorphine at 186 ng/mL

Buprenorphine glucuronide at 368 ng/mL

Naloxone at <100 ng/mL

Oxycodone at <10 ng/mL

Noroxycodone at <10 ng/mL

Oxymorphone at <10 ng/mL

Noroxymorphone at 65 ng/mL

Previous collections revealed similar patterns








Nornaloxone = Noroxymorphone!

noroxymorphone | nornaloxone

noroxycodone

oxymorphone

naloxone

oxycodone

Final Interpretation

Questions For The Panel?

Documents

Interpretation Of Urine Drug Testing Results For Pain … · 2019. 3. 31. · Structured Method For Proper Drug Testing Interpretation Example: “Mr. Smith was found to be positive