Laboratory Challenges in Clinical
Toxicology of Pain Management
By Michael (Rusty) Nicar
&
Marc McCain
Clinical Tandem Mass Spectrometry:
Cutting Edge Technology for the Clinical Lab
Children’s Medical Center October 2010
Texas Medical Board Rules 2010
What is Chronic Pain: “a state in which pain
persists beyond the natural course of an acute
disease or healing of an injury.”
Appropriate drug therapy:
“recognized by consensus.”
“A physician may require laboratory tests for
drug levels upon request.”
How Many Patients Have Chronic Pain?
1 out of 4 Americans have
recurrent pain
1 out of 10 have pain of
at least 1 yr duration
Treatment of Choice for Chronic Pain
CHRONIC OPIOID Rx
Hydrocodone is the most prescribed
drug in the USA. Others used for pain:
morphine, codeine, fentanyl,
oxycodone, hydromorphone,
oxymorphone, meperidine, methadone.
Why Do Pain Doctors Drug Test
Concerns:
Drug Diversion
(majority of overdose deaths in W. Virginia were due to
diversion of opioids, JAMA 2008 300:2613)
Taking non-prescribed
or illegal drugs
Taking more than
the prescribed dose
Overdose
Estimated Number of Emergency
Department Visits in 2006:
Opioids – 250,000
Acetaminophen – 50,000
NSAIDS – 35,000
What Medications Do Pain Patients Take
What Are Patients Taking
CT: Cymbalta, Lyrica, Fentanyl, Hydrocodone
GG: Flexeril, Rozerem, Lortab, Allegra, Relafen
TK: Duragesic, Percocet, Ambien
RT: Lyrica, Norco
LV: Zantac, Carisoprodol, Wellbutrin, Topamax, Ambien,
Hydrocodone, Celebrex, Flomax, Lexapro, Morphine,
Baclofen
What Are Patients Taking
RR: Oxycontin, Percocet, Topamax, Metformin,
Foltix, Lasix, Singulair, HCTZ, Nifedapine,
Diovan, Premarin, Zetia, Omega 3
ML: Sirolimus, Cellcept, Metoprolol, Methadone,
Effexor, Synthroid, Norvasc, Lisinopril,
Allegra, ASA
OP: Skelaxin, Robaxin, Norco, Methadone
FH: Fentanyl, Tramadol
Why Do Pain Doctors Drug Test
State regulators require physicians to test
patients during pain management.
Testing improves the Quality of Care.
Testing is the Standard Of Care for pain
management.
Pain Physician 11:S5-S62, 2008.
Journal of Pain 10:113-130, 2009.
Laboratory Monitoring
“Standard of Practice” for laboratory
monitoring of pain patients is urine drug
testing.
Because it was readily available, rapid,
non-invasive, and inexpensive.
Not because it is the best scientifically.
Urine Drug Positives
Study from Johns Hopkins in 11,000 chronic pain patients
confirmed positives in theiurine specimens (JAT 2008):
Amphetamines 2%
Barbiturates 3%
Benzodiazapines 22%
Cannabis 9%
Carisoprodol 3%
Cocaine 3%
Fentanyl 4%
Meperidine 1%
Methadone 11%
Opiates 82%
Propoxyphene 4%
Drug Screen Results in Dallas
At CHOICE Laboratory, I see the
following distribution on AU urine
drug screens:
Negative – 25%
Opiate – 50%
Opiate + Oxycodone – 16%
Illicit Drug Use Among Pain Patients
Patients must also be tested for illicit drug use.
A study in Kentucky reported the following
percentage of pain patients using:
Marijuana – 11% (13% of females, 7% of males)
Cocaine – 5%
Methamphetamine – 2%
Pain Physician 9:215-226, 2006
Illicit Drug Use in Dallas Patients
At Choice Labs:
Marijuana (THC positives confirmed) – 8% *
Cocaine – 2% *
Methamphetamine – 1%
*no false positives by AU immunoassay screen
Limitations of Immunoassays
Crossreactivity of the antibody
Can’t identify specific drugs
Opiate = morphine + codeine + hydrocodone
Cut-offs (Qualitative)
Commercial assays come with cut-offs
Limitations of Immunoassays
False Positives due to crossreactivity:
Cannabinoids – Protonix, Daypro
Methadone – diphenhydramine, propoxyphene
PCP – meperidine, dextromethorphan
Oxycodone - Oxymorphone
Instrumentation
Immunoassays for single drugs can be quantitative
and the Beckman Olympus AU has a semiquantitative mode for drug classes (ie Opiates,
Benzos) – but these assay still use antibodies and
have limitations.
Confirmation instrument of choice for
pain management labs:
LC-MS/MS
Why LC-MS/MS
SPECIMEN PREPARATION:
LC-MS/MS requires significantly less
specimen prep than GC/MS
GC/MS – treatment and derivatization
LC-MS/MS – little or no treatment and
no derivatization
“Dilute & Shoot”
Why LC-MS/MS
SPECIMEN VOLUME:
LC-MS/MS requires significantly less
specimen than GC/MS
GC/MS – 2-5 mLs
LC-MS/MS – 0.2-1 mL
Why LC-MS/MS
SENSITIVITY
LC-MS/MS requires dilution of
specimens while GC/MS requires
specimen concentration
GC/MS Opiate LOD = 100 ng/mL
LC-MS/MS Opiate LOD = 25 ng/mL
Why LC-MS/MS
Single scan determination
of many drugs in minutes.
But…..CPT codes are for “assays” and
Medicare pays for each assay – not
for each drug measured.
The Pain Drug Screen
Amphetamine
Barbiturates
Benzodiazepines
Cannabinoids
Cocaine
MDMA
Methadone
Opiates
PCP
Propoxyphene
Oxycodone
TCAs
Creatinine
Alcohol
Cotinine
Buprenorphine
Adulterants
The Pain Drug Confirmations
Amphetamine, Methamphetamine, MDA, MDMA, MDEA
Buprenorphine, Norbuprenorphine
7-aminoclonazepam, Hydroxyalprazolam, Oxazepam, Lorazepam,
Nordiazepam, Tamazepam
Carisoprodol, Meprobamate
Benzoylecgonine
Methadone, EDDP
Propoxyphene, Norpropoxyphene
The Pain Drug Confirmations, cont
Morphine, Codeine, Hydrocodone, Hydromorphone
Oxycodone, Oxymorphone, 6-MAM
Amitriptyline, Nortriptyline, Imipramine, Desipramine,
Doxepin, Desmethyldoxepin, Cyclobenzaprine,
Clomipramine, Norclomipramine
Fentanyl
Tramadol, Meperidine, Normeperidine
Amobarbital, Butabarbital, Pentobarbital, Phenobarbital,
Butalbital, Secobarbital
THC-COOH
Children’s Medical Center 2010
Thank You.