toxicology urine testing for drugs of abuse

• Drugs that are taken for non-medicinal reasons • Repeatedly and deliberately used in a way other than prescribed or socially sanctioned. • Usually a single urine specimen is tested for multiple drugs. • Testing can be requested by governmental, industrial, educational, and sports agencies.

• Pre-employment condition • Testing of current employees in certain circumstances • Military • Monitoring of patients in drug rehabilitation programs • Parolees • Athletes • Patient presenting to the ER with an unknown overdose • Organ transplant candidates • Pain management clinics • Psychiatric programs

• Only detects recent use • Does not differentiate casual from chronic use • Cannot determine: • Degree of impairment • Dose of drug taken • Exact time of use • Similar drugs may result in a positive test • Immunoassays are typically used for screening tests • Specimens above an established cutoff concentration (threshold) are considered presumptively positive. **** • Specimens below the cutoff are considered negative. • Positive cases must be confirmed by a more definitive test (GC-MS)- confirmatory method

• Assessment of drugs of abuse is important to: • Determine the agent responsible for an overdose and provide timely treatment • Identify drug abuse in non-overdose situations to provide treatment for addiction • Typically done using a screening test. • Only detects recent drug use • Users can avoid detection with short period of abstinence • A positive result can not differentiate between a single casual use and chronic abuse • A positive result also does not tell you the time frame the drug was taken or the dosage. • Screening tests typically use immunoassays • Gas chromatography/Mass spectrometry is the confirmatory method for most analytes

The following are drugs that are usually tested with urine drugs of abuse cassettes: • Methamphetamines • Cocaine • THC • Methylenedioxymethamphetamine (MDMA) • Methadone • Morphine • Benzodiazepines • Tricyclic Antidepressants (TCAs) • Barbiturates • Phencyclidine (PCP) • Amphetamines • Oxycodone Positive results can be confirmed by gas chromatography/mass spectrometry (GC/MS)

• CNS stimulants • Therapeutic drugs used for: • Narcolepsy • Attention Deficit/Hyperactivity Disorders (ADHD) • High abuse potential • strong psychological dependence and mild physical dependence • Tachycardia, increased blood pressure, restlessness, irritability, insomnia, personality changes - Depression, impaired memory and motor skills • Amphetamine-like compounds are common in allergy and cold medications • Metabolized in the liver and eliminated unchanged in the urine.

• Immunoassay used as screening test - Some designer amphetamines may not be picked up (use a more sensitive method) - Similar drugs may produce a positive result Ex. Pseudoephedrine (cold medication) • All presumptive positive results should be confirmed using GC-MS or LC-MS/MS

• Commonly referred to as ecstasy • Primarily taken orally • Less frequently: inhaled, injected or smoked • Majority is eliminated by hepatic metabolism • 20% eliminated unchanged in urine • Half-life of 8-9 hours • Duration of effects is about 3.5 hours - Hallucinations, euphoria, empathic and emotional responses, increased visual and tactile sensitivity

• Group of compounds found in the plant Cannabis sativa • Used as a medicinal and psychotropic agent • Euphoria, distorted perceptions, relaxation, and a feeling of well-being • Psychoactive compounds found in marijuana. - Most potent and abundant is THC • THC is lipophilic • Distributes to highly vascularized tissues within minutes of inhalation of marijuana • Quickly removed from circulation into brain and fat tissue • Then redistributes back into blood stream and undergoes hepatic metabolism - This causes slower elimination* • THC is metabolized by the liver into several compounds that are then excreted in the urine. • The major urinary metabolite (THC-COOH) can be detected for up to: * 5 days - single use * 4 weeks - chronic, heavy use • THC-COOH can also be detected in urine as a result of passive inhalation -Standards have been established for urinary concentrations to differentiate between passive and direct inhalation • Analysis: • Immunoassay - Use antibody reagent against THC-COOH metabolite • Chromatographic methods - GC-MS/MS or LC-MS/MS

• Local anesthetic at therapeutic concentrations - Used in nasal surgery - local anesthesia and vasoconstriction - In ophthalmology - dilate pupils • One of the most common illicit drugs of abuse • Potent CNS stimulator at higher concentrations - Elicits sense of excitement and euphoria • Frequently taken with ethanol - 18-25-fold increase in toxicity compared to taking COC alone. • Taken intravenously present the greatest hazard, followed by smoking • Product of liver metabolism (benzoylecgonine) can be found in urine up to: * 3 days - single use * 20 days - chronic, heavy use • Analysis: • Immunoassay • GC-MS or LC-MS for more polar metabolites

• Analgesic, sedative, and anesthetics • Derived from or related to substances from the opium poppy • Naturally occurring forms: • Opium • Morphine • Codeine • Chemically modified forms: * Heroin * Oxycodone • Synthetic forms: • Methadone * Fentanyl • High abuse potential - Physical and psychological dependence with chronic use • Genetic variation can play a role in metabolism - Low CYP2D6 activity (poor metabolizers) - may receive inadequate analgesia ( need more to have same effects) - High CYP2D6 activity (ultrarapid metabolizers) - risk for adverse responses( need less to have same effect) • With acute overdose: - Respiratory acidosis - Myoglobinuria - Increased CK-MB, troponin ( cardiac markers) • Treatment of overdose - naloxone*****

• Illicit drug • Stimulant, depressant, anesthetic and hallucinogenic properties • Adverse effects: - Agitation, hostility, paranoia • Can produce profound analgesia at anesthetic doses - awake but incapacitated, with limited voluntary limb movement • Lipophilic • Quickly distributes into fat and brain tissue • Slow elimination • Can be detected up to 30 days after abstinence in chronic, heavy users

• First intestinal discharge from newborns - Begins to form during 2nd trimester and continues to accumulate until birth - Can be used to detect drugs taken by the mother during pregnancy. • Limitations: - Low-birth-weight infants may have delayed passage of meconium and could be missed - Sticky material that is hard to work with in the lab • Can be analyzed using immunoassay and confirmed with LC-MS/MS or GC-MS • Drugs that are tested for include: - Cocaine, opiates, cannabinoids, amphetamines, ethanol, PCP

• Analysis of saliva Advantages: • Non-invasive if collection has to be monitored - Minimizes risk of adulteration • Fear, anxiety, and discomfort of drawing blood are diminished Disadvantages: • Window of detection is short compared to urine • Metabolites may poorly distribute in fluid • pH may affect deposition in fluid • Small volume obtained • Analysis: GC-MS, LC-MS, LC-MS/MS

• Easily obtained and not easily altered or manipulated • Long detection window (months to years) • Sensitive methods of analysis are needed due to relatively low concentrations in hair - GC-MS - method of choice • A washing step is usually done to help differentiate between passive exposure (environmental contamination) and active consumption.

• Drugs may be excreted in sweat. • Sweat patch collection devices can be worn for several days to several weeks • Resemble an adhesive bandage • If a drug is present it will accumulate on the absorbent pad • Drug use can be monitored over an extended period of time without having to collect multiple urine samples.