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Urine Drug Testing Methods3-5 Type of Test Logistics Pearls • Inexpensive • High sensitivity, low specificity (higher potential for false positives) Initial Screening Test: • Fast • Opiate screen not sensitive for semisynthetic (e.g. oxycodone) or Immunoassay • Widely available synthetic opioids (e.g. fentanyl) Confirmatory Test: Gas chromatography-mass • High sensitivity, high specificity • Expensive spectrometry (GCMS)+ or • Expensive • Time consuming Liquid chromatography-mass • Detects medication even if concentration is low spectrometry (LCMS) + GCMS is considered the criterion standard for confirmatory testing; Immunoassay tests have high predictive values for marijuana and , but lower predictive values for opiates and

Urine Drug Testing Specimen Validity3-4 Normal Characteristics of a Urine Sample3-5 • Urine samples that are adulterated, substituted, or diluted may Temperature within 4 minutes of voiding: 90-100⁰F avoid detection of drug use4 pH: 4.5-8.0 • Urine collected in the early morning is most concentrated and Creatinine: > 20 mg/dL most reliable Specific gravity: > 1.003 • Excessive water intake and diuretic use can lead to diluted urine Nitrates: < 500 mcg/dL samples (Creatinine < 20) 3-4 • THC assays are sensitive to adulterants (e.g. Visine eyedrops) Volume: ≥ 30 mL

4 Source: https://www.healthquality.va.gov/guidelines/Pain/cot/VADoDOTCPGProviderSummary022817.pdf Urine Drug Testing (UDT) Federal Work Place Cut Off Values3-9 Initial Drug Test Level Confirmatory Drug Test Detection Period After Confirmatory Test Analyte3,7 (immunoassay) (ng/mL) Level (GC–MS) (ng/mL) Last Dose (Days)* Marijuana 2-8 single use 50 15 THCA Metabolites 20‑30 chronic use+ Cocaine Metabolites 300 150 BEG 1–3 2–3 days opiates Opioid Metabolites 2000§ 2000§ Codeine, Morphine, 6-MAM 3–5 minutes heroin 12–24 hours 6-MAM

Regular UDT Oxycodone N/A N/A 2–4 , Amphetamines 1000 500 1–3 MDMA, MDA, MDEA Methamphetamine Incomplete data 500 3–4 Extended UDT 3 short-acting Benzodiazepines 300 200 30 long-acting 1 short-acting Barbiturates 300 200 21 long-acting Methadone 300 200 EDDP 3–6 Alcohol N/A N/A EtG, EtS 12 hours THCA = delta-9-tetrahydrocannabinol-9-carboxylic acid; BEG = benzyolyecgonine; 6-MAM = 6-monoacetylmorpine; EDDP = 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EtG = ethyl glucuronide; EtS = ethyl sulfate; * Detection time for most drugs in urine is 1-3 days; + Long-term use of lipid-soluble drugs (THC, diazepam, ) can be detected for a longer period of time; § Testing levels for opiates were raised from 300 ng/mL to 2000 ng/mL to reduce detection from foods containing poppy seeds 5 Agent Summary of Agents Potentially Contributing to False Positives3-8 Marijuana • dronabinol • NSAIDs* • hemp foods: tea, oil+ metabolites • efavirenz • proton pump inhibitors Cocaine metabolites • leaf teas • topical anesthetics containing cocaine • dextromethorphan • levofloxacin • poppy seeds • rifampin Opioid metabolites • flouroquinolones • ofloxacin • poppy oil • quinine

• • • • ranitidine Amphetamines/ • • • l-methamphetamine • • Methamphetamine • brompheniramine • (OTC nasal inhaler) • phenyl‑propanolamine • (high rate of false • • fluoxetine • • • positives) • • isometheptene • MDMA • • trimethobenzamide • • • •

Benzodiazepines • oxaprozin • sertraline Barbiturates • ibuprofen • naproxen • chlorpromazine • doxylamine • thioridazine Methadone • • ibuprofen • verapamil • diphenhydramine • Alcohol • mouthwash • short-chain alcohols • OTC cough products (isopropyl alcohol) * NSAIDs resulting in false-positive for marijuana mainly consist of ibuprofen and naproxen and modern tests do not result in false positives ; + THC concentrations in hemp products are low enough to prevent positive immunoassay results

6 Interpreting Urine Drug Testing2,3-5 Drug or Class Expected Results Considerations • Testing for ETOH metabolites, ethyl glucuronide or ethyl Alcohol Alcohol sulfate, can identify alcohol up to 80 hours after consumption Immunoassay–amphetamines, • Immunoassay tests are highly cross-reactive; therefore or MDMA Amphetamines confirmatory testing is required and can identify which Confirmatory–amphetamines, amphetamine is present methamphetamines or MDMA • Immunoassays for benzodiazepines have a 28% overall false Immunoassay–unconjugated negative rate oxazepam or its metabolites Benzodiazepines • Confirmatory testing is needed when use is expected or Confirmatory–alprazolam, diazepam, suspected (alprazolam, clonazepam and lorazepam often not clonazepam, lorazepam, etc. detected by immunoassay) Barbiturates Immunoassay–barbiturates • N/A • Cocaine’s primary metabolite, BEG, has low cross-reactivity Immunoassay–cocaine or with other substances and is highly predictive of cocaine use Cocaine metabolites benzoylecgonine (BEG) • A positive result should be interpreted as recent exposure to cocaine

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Interpreting Urine Drug Testing2,3-5 Drug or Class Expected Results Considerations Opioids or “opiates”- Natural (from opium) • Immunoassays for “opiates” are responsive to morphine and codeine Opiates Immunoassay–positive Codeine but do not distinguish which Confirmatory–codeine, possibly (Tylenol # 2,3,4) • Codeine is metabolized to morphine and small quantities of morphine & hydrocodone hydrocodone Morphine (Avinza, Opiates Immunoassay–positive • Immunoassays for “opiates” are responsive to morphine and codeine Embeda, MS Contin, Confirmatory–morphine, but do not distinguish which Kadian) possibly hydromorphone • Morphine (<10%) may be metabolized to hydromorphone Opiates Immunoassay–positive • 6-MAM is pathognomic for heroin use, detection 12–24 hrs Heroin Confirmatory–heroin (6–MAM), • Heroin is metabolized to morphine morphine, possibly codeine Opioid Metabolic Pathways Codeine  Morphine  6-MAM  Heroin  <15%  <10% Hydrocodone  Hydromorphone Oxycodone  Oxymorphone

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Interpreting Urine Drug Testing2,3-5 Drug or Class Expected Results Considerations Opioids-Semisynthetic (derived from opium) Hydrocodone (Lorcet, Opiates Immunoassay–positive • “Opiates” immunoassay may detect semisynthetic opioids Lortab, Norco, Vicodin) Confirmatory–hydrocodone, possibly hydromorphone o hydrocodone > hydromorphone > oxycodone Hydromorphone Opiates Immunoassay–may be positive • Negative result does not exclude use and confirmatory testing (Dilaudid, Exalgo) Confirmatory–hydromorphone (GC/MS) is required • Hydrocodone is metabolized in small amounts to Opiates Immunoassay–may be positive Oxycodone (Roxicet, hydromorphone, both may be found in urine Oxycodone Immunoassay–positive OxyCotonin) • Oxycodone is metabolized to oxymorphone, both may be Confirmatory–oxycodone possibly oxymorphone found in urine Oxymorphone Oxycodone Immunoassay–positive • Hydromorphone and oxymorphone use does not result in (Opana) Confirmatory–oxymorphone positive screens for hydrocodone and oxycodone, respectively Opioids-Synthetic (man-made) Fentanyl GC/MS–fentanyl and norfentanyl Meperidine (Demerol) GC/MS–normeperidine, possibly meperidine • Current “opiates” immunoassays do not detect synthetic Methadone Methadone Immunoassy–positive opioids (Methadose) GC/MS–methadone, EDDP • Confirmatory testing (GC/MS) is needed Propoxyphene Propoxyphene Immunoassy–positive (Darvon, Darvocet) GC/MS–propoxyphene & norpropoxyphene Confirmatory testing: Chromatography (gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC/MS)) Note: Each facility may have its own order sets and lab policies and procedures. Contact your lab for additional details.

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