Amphetamines

The term amphetamines refer to a class of compounds that are structurally related to amphetamine (1-phenyl-2-aminopropane). Amphetamines are included in a broader class of compounds called phenylisopropylamines. Specimen must also contain amphetamine at a concentration of greater than or equal to 200 ng/mL. Test for 6-hM in the specimen. Conduct this test only when specimen contains morphine at a concentration greater than or equal to 2,000 ng/mL.

Included in this class are amphetamine and its N-methyl derivative, methamphetamine. The only analyzes that may he reported under the DHHS/DOT drug-testing program, however, are amphetamine and methamphetamine.

Medicinal Use and Abuse

Amphetamine and methamphetamine, like many phenylisopropylamines exist as stereo-isomers. The pharmacological activity of the drug depends on its stereochemistry. Currently in the United States, amphetamine is only approved for use in narcolepsy, attention-deficit disorder, attention deficit hyperactivity disorder (ADHD), and learning disorders associated with fetal alcohol syndrome. In the United States, pharmaceutical amphetamine drugs contain either only d-amphetamine (Dexedrine, Dextrostat) or a 3:1 mixture of d- and 1-amphetarnine, respectively (Adderall). Dextromethamphetamine (d-methamphetamine) has strong central nervous system ICES) stimulant activity and is the amphetamine analog most subject to abuse. Desoxyn (Schedule II) is pure d-methamphetamine and is infrequently prescribed for attention-deficit disorder with hyperactivity.

Table 15-2 Drugs Containing Methamphetamine and/or Amphetamine

Both Desoxyn and Methadrine metabolize to d-amphetamine and d-methamphetamine. The l-form of methamphetamine, which produces primarily peripheral effects, is available OTC in the Vicks and other generic nasal inhalers. Prescription drugs that contain methamphetamine and or amphetamine are provided in Table 15-2.

D-Methamphetamine abuse is widespread. Methamphetamine labs appear nationwide in primarily rural settings. Street names for the hydrochloride salt include Speed and Crank. The drug may be administered orally in capsules or tablets, snorted, or smoked. This started particularly on parts of the West Coast and in Hawaii and is spreading in what some consider being epidemic fashion. A form of methamphetamine^5 known on the street as ice or Crystal, is prepared by creating a saturated solution of methamphetamine hydrochloride in hot water and letting the solution cool in a refrigerator. Large crystal form, much like rock candy forms when a sugar-saturated solution cools.

The principal effects of methamphetamine are similar to cocaine. These include increased feelings of energy and alertness, self-confidence, and mental ability, in addition to anorexia and possible irritability. Much like cocaine, smoked or intravenous methamphetamine produces more intense CNS stimulant effects with a shorter onset of action. Tolerance to the drug is profound. Abusers have been known to administer up to 200 times the therapeutic dose of 5 mg. Severe depression, which may lead to suicide, can occur on withdrawal.

Metabolism and Analytical issues

About half a dose of methamphetamine is excreted unchanged in the normal urine within 24 h. Acidic urine greatly facilitates its excretion, and up to 76% of a dose may be excreted unchanged.  In alkaline conditions, only 2% of a dose of methamphetamine is excreted unchanged. Less than 10% of a dose of methamphetamine is excreted as amphetamine in normal urine. In normal urine, approximately 70% of a dose of amphetamine was excreted in the 24-h urine with 30% as unchanged drug. Excretion was increased to 74% under acidic conditions and reduced to 1% in alkaline urine. Because pH has such a profound effect on the excretion of amphetamine and methamphetamine, detection times in urine may be quite variable. In general, amphetamine and methamphetamine can be detected for 24 to 48 h after use in a normal urine specimen.

Immunoassays used in DHHS-certified laboratories are targeted toward d-amphetamine, d-methamphetamine, or both. Those targeted at d-methamphetamine have generally less than 5% cross-reactivity to the l-isomer and cross-reactivity to the hydroxylated sympathomimetics (e.g., ephedrine and pseudoephedrine).

Gas chromatography-mass spectrometer GC-MS) confirmation tests will distinguish amphetamine and methamphetamine from other phenylisopropylamines. However, routine GC-MS procedures do not distinguish between the d – and l-isomers of the amphetamines. This becomes important when an individual is taking drugs excreted as l-amphetamine and l-methamphetamine. Selegiline (Eldepryl), an anti-Parkinson drug, is metabolized to Methamphetamine and l-amphetamine. I-Isomers of amphetamine and methamphetamine can be detected in the urine following the use of a Vicks nasal inhaler.

To assist in the interpretation of methamphetamine positive results, it is recommended that the MRO request d- and l-isomer testing (also known as chiral analysis be performed before reporting a positive test result to distinguish potentially illegal drug use from legal drug use. There are no official federal requirements for the interpretation or reporting of d-, I-isomer differentiations. However, the recommendation that chiral identification of l-methamphetamine at greater than 80% of the total methamphetamine concentration is consistent with the use of Vicks which is generally accepted in the MRO practice. There are some prescription drugs that do not contain amphetamine or methamphetamine, do metabolize to amphetamine and methamphetamine and may end up giving positive result. Drugs which metabolize in this way are given in Table 15.3.

In September 1990, false positive methamphetamine results were reported when it was formed in vitro using a particular GC-Ms result. It was also learnt that methamphetamine could be produced in some specimens which had very high concentrations of ephedrine or pseudoephedrine when subjected to a particular or specific chemical derivatization process while confirming. However, amphetamine was not similarly produced. So, the confirmatory reporting requirements changed so that at least 200 ngknL of amphetamine, in addition to 500 ng/mL of methamphetamine must be present to report a positive methamphetamine confirmation result. Since these changes went into effect, no further problems with methamphetamine analysis have been reported. This change has been incorporated into the revised DHHS guidelines and D01 regulations.

Table 15-3 Drugs That Metabolite to Amphetamine and Methamphetamine

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