False Positive Methamphetamine

In 1993, Hornbeck et al. (44) demonstrated that methamphetamine can be generated from high levels of pseudoephedrine or ephedrine in injection ports at a temperature of 300°C after derivatization with 4-CB, HFBA, and TPC. They investigated the effect of changing conditions and concluded that the most important conditions for this thermal conversion are the high injector temperature and high concentrations of pseudoephedrine or ephedrine. In their experiments, the highest amphetamine concentration obtained was less than 50ng/mL. The heptafluorobutyryl derivative of ephedrine has also been shown to give methamphetamine peak interferences because of contaminants in the derivatizing reagent (45). Occurrence of false-positive results in the Federal Drug Testing Program because of generation of methamphetamine resulted in the implementation of a requirement that in order to report a positive methamphetamine the metabolite amphetamine must be present at a concentration of 200 ng/mL or higher. This concentration would be lowered to 100 ng/mL in conjunction with the proposal to lower the cutoff concentration for confirmation to 250 ng/mL (4). In one study, 90% of specimens collected from volunteers ingesting methamphetamine at concentrations mimicking occasional use had amphetamine concentrations below 200 ng/mL even though most had methamphetamine concentrations above 500 ng/mL (46).

Recommendations to prevent generation of methamphetamine include lowering the injector temperature and periodate pretreatment of samples. ElSohly et al. (47) showed that periodate treatment eliminated formation of methamphetamine by 1,000,000 ng/mL of pseudoephedrine, ephedrine, phenylpropanolamine, and norpseudoephedrine by selectively oxidizing these compounds in the presence of amphetamine and metham-phetamine. They used 0.35 M sodium periodate for 10 min at room temperature. SAMHSA-certified laboratories that have an oxidation step in their amphetamine confirmation procedure are required to monitor the effectiveness of the procedure in each confirmation batch by analyzing a quality control sample containing a high concentration of sympathomimetic amines (43).

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