Emerging Issues in Drug Testing Greg Skipper, MD Director, Professional Health Services Promises Treatment Centers Los Angeles, CA gskipper@promises.com 310-633-4595

Drug Testing is Effective and Underutilized When testing is frequent, random and tied to immediate moderate consequences drug use is deterred.

Long-Term PHP Drug Test Results

Difficult Cases Patient prescribed hydrocodone Urine test negative for opioids Urine test positive for hydromorphone only? Oxymorphone? Codeine?

Difficult Cases

Difficult Cases Patient prescribed oxycodone Urine test negative for opioids Urine test positive for hydrocodone Oxymorphone? Codeine?

Anomalous observations of hydrocodone in patients on oxycodone. West R et al, Clin Chim Acta. 2010 Aug 27. BACKGROUND: Oxycodone preparations are known to have small amounts of hydrocodone as an impurity estimated to be <0.1%. We established the concentration of unexpected hydrocodone in patients taking oxycodone. METHODS: 30,000 pain patients CONCLUSIONS: When oxycodone is >100,000ng/ml, hydrocodone should be <1500ng/ml. When oxycodone is <100,000ng/ml then hydrocodone should be <500ng/ml. Values greater than these indicate non-prescribedhydrocodone use. Clinicians and laboratories testing urine for drugs should be aware of the possibility of low concentrations of hydrocodone in the urine of patients taking high doses of oxycodone.

Difficult Cases Patient prescribed Valium Urine test positive for oxazepam only Temazepam

Difficult Cases Patient on xanax (alprazolam) or Klonopin (Clonzaepam) Urine test negative for benzo’s?

Sensitivity vs Specificity Are they always mutually exclusive? Highly sensitive More prone to false positive? Highly specific More prone to false negative?

Screening vs Confirmation Tests Immunoassays, ELISA, EMIT, DRI, Dipstick Tend to be highly sensitive Not so specific Confirmation GC/MS, LC/MS, LC/MS/MS Highly specific Not so sensitive (because of restricted panel)

Matrices

MRO function Is there a cause for positive other than illicit use? Legitimate prescription False positive – at least two types

Legitimate Use? Coca tea? Cocaine positive from sex? ENT procedure? Hemp oil? Hemp cereal? Hemp cosmetics? Hemp granola bars? Hemp lip balm? Sprained ankle and was given heroin while visiting Great Britain? THC? Ever legal in US? Passive inhalation Poppy seeds

Poppy Seeds Over 1,000 species of poppy seeds Used in cooking Baking Salad dressings Curry sauces Morphine level >1,000, >2,000, >5,000, >15,000 ???? Urine concentration can be a clue

Accidental Exposure Marijuana brownie Someone else’s medication Took pill and didn’t know what it was Drank punch and didn’t know it had alcohol in it Vacuuming up someone else’s cocaine and turned vacuum clearner on reverse and blew it into the air

Crossreactivity

Positive Amphetamine due to l-isomer Vics inhaler, selegiline, EMSAM patch D & L Isomer test >80% l-amphetamine consistent w/ Pseudoephedrine converted to amphetamine inside the GC/MS machine Retest

Dilutes Creatinine <20mg/dl and sp gr <1.003 Creatinine <20 but >10 mg/dl can be from innocent excess water Creatinine <10mg/dl but >5mg/dl not likely innocent Creatinine <5mg/dl probably substitution Creatinine <2mg/dl definitely substituted

What to do? Creatinine <20 but >10 mg/dl can be from innocent excess water Warn, observed, obtain hair/nails or saliva test Creatinine <10mg/dl but >5mg/dl not likely innocent Hair/nail, saliva, observed, evaluation Creatinine <5mg/dl probably substitution Assume substitution, verify observed, retest sample

Emerging Technologies Quick Test Kits Better confirmation tests: LC/MS/MS More extensive testing panels Increased Use of Flex Testing Improved testing for ethanol (EtG, EtS, etc) Devices: TAD, SCRAM, Soberlink

Hair Testing

Nail Testing Good alternative to hair testing Similar repository window Less prone to adulteration from chemicals Thicker than hair

Saliva Testing DHHS - 5 DRUGS, ALCOHOL SIMILAR TO PLASMA INCREASINGLY USED (ie dilute urines)

Sweat Testing DHHS - 5 DRUGS PAROLE/PROBATION Less invasive than hair testing

New Alcohol Monitoring Technologies

In the beginning… Blood alcohol Breath alcohol Urine alcohol GGT, MCV Limitations when used for alcohol monitoring GGT, MCV Carbohydrate Deficient Transferrin

Current Technologies Random field breathalyzer Multiple daily ID home breathalyzer Transcutaneous alcohol monitoring New markers EtG – EtS – PEth Urine – Hair/Nails – Saliva – Blood

Frequent / Random Breathalyzer 24/7 Program in South Dakota Random testing field programs BAT Mobile

24/7 South Dakota House bill 1072 Rules: Results - 2007 Type, frequency, time, location, fees ($1 for each breath test), consequences Usually twice a day on site in local police dept Results - 2007 1,021 participants, 165,456 tests, 359 no shows = 99.8% show rate Of 165,456 tests 534 failed tests

24/7 South Dakota Of 165,456 tests 534 failed tests Rate of improvement for individuals - good

Positive ID Home Breathalyzers New home breathalyzer technologies MEMS 3000 Smart Start In-Hom Mobile Breath

MobileBreath®

Soberlink Smart Phone Compatible and Required: Requires Android OS 2.2 or higher, or Blackberry OS 5.0 or higher (device must be Bluetooth enabled). Apple iPhone compatibility coming soon. Photo Identification: Guarantee's the identity of the user. Facial recognition coming soon. Fuel Cell Sensor: Provides highly accurate and reliable results. DIMENSIONS: Product Height: 4.75" (121mm) Product Width: 1.5" (38mm) Product Depth: 2.875" (73mm) WEIGHT: Product Weight: 6oz (190g) WARRANTY: 1 Year Limited Warranty

Soberlink

Transcutaneous Monitors SCRAM TAD

Intermittent Transcutaneous Alcohol Monitoring www.alcoholmonitoring.com – to locate provider

Unique Alcohol Metabolites Ethylglucuronide (EtG) Urine Hair/Nails Saliva

Urine EtG (and EtS) 1-4 days possible duration Normalization important (100/uCreat) x uEtG = Normalized EtG Important to warn about things to avoid Foods, mouthwash, handgel, etc.etc. May be important to have participant sugar fast (4-6 hours) before submitting sample Juices, fruits, etc contain small amounts etoh

Alcohol Metabolites Phosphatidyl Ethanol (PEth) Blood A group of phospholipids formed by alcohol on cell membranes - phospholipase D Positive only after significant alcohol exposure (approx 7 drinks over a week) Stays positive (>20ng/ml) for 2-3 weeks Level correlates well with amount of alcohol consumed

Alcohol Metabolites Phosphatidyl Ethanol (PEth)

Combination Strategies Using PEth to confirm drinking following positive EtG/EtS when drinking denied Study: 18 positive EtGs Finding # % Conclusion Admitted drinking after positive EtG/EtS 8 44 Drinking Admitted drinking after PEth explained 3 17 Admitted drinking after positive PEth 1 6 Denied drinking after positive PEth Denied drinking - negative PEth 5 28 Not Drinking

Settings / Strategies Normalize values to creatinine of 100md/dl (labs should automatically make this calculation) Have participants sign consent regarding their responsibility to avoid alcohol Re-advise to avoid all alcohol (including ripe fruits, juices, anything containing sugar) on day of test.

HOPE Probation HOPE probationers have the most serious felony drug and crime problems and are identified as likely to violate their conditions of community supervision HOPE utilizes intensive random drug testing for up to 6 years Responds to detected violations of probation (drug use, missed probation meetings, etc.) with clear, swift, short-term sanctions

Randomized Control Trial of HOPE vs. Standard Probation In one-year period, HOPE probationers were: 55% less likely to be arrested for a new crime 72% less likely to use drugs 61% less likely to skip appointments with their supervisory officer 53% less likely to have their probation revoked HOPE probationers were sentenced to, on average, 48% fewer days of incarceration than the control group

HOPE Drug Test Results