As indicated in the previous section, limitations of the federal workplace drug-testing program pretty well define the considerations that must be made regarding the conduct of the analysis. In the less constrained environment of the postmortem laboratory, issues such as thermal liability of compounds and low concentrations are of significant concern. Although this is a legitimate concern, in the case of the amphetamines the compounds are stable, and in relatively high concentrations play only a minor role for analysis of amphetamines. One other consideration, however, is the practical ability to analyze many different compounds at the same time from a single sample. Such considerations cause decisions that compromise conditions to maximize the ability of the method to identify many different compounds. Although conditions are often such that procedures used in those circumstances do not have the lower limits, linear range, and recovery seen when procedures are targeted to only 2 analytes, the nature of the samples of interest in postmortem analysis allows for accurate and reliable analysis.
Although amphetamines are relatively straightforward to analyze as compared to some other drug classes, their chemical nature poses a number of analytical challenges. A clear example of that comes from the so called “methamphetamine artifact” seen some years ago when a small number of samples was reported as positive for methamphetamine under the federal workplace drug-testing program. These samples met the criteria for MS identification of a compound, in this case methamphetamine, at an indicated concentration above the cutoff established for methamphetamine. Investigation of the problem resulted in a number of different actions to prevent recurrence of the problem. One was the policy that to report a sample as positive for methamphetamine it must also contain amphetamine at or above 200ng/mL. Given the metabolism of methamphetamine, it makes good sense to expect the presence of amphetamine; however, the expected amount of amphetamine for a sample that contains methamphetamine at 500ng/mL would be considerably below 200ng/mL. This is exemplified in a report that measured the concentrations of amphetamine and methamphetamine following administration of methamphetamine, which showed 90.296 of samples did not meet the >200 ng/mL requirement. Another study described the large number of samples that did not meet the revised guidelines despite their use of methamphetamine. In addition to the administrative change in the reporting requirements, a change was made by some laboratories to eliminate the ephedrine and pseudoephedrine in a sample prior to analysis to eliminate the interference. This involved the use of periodate to chemically break down the ephedrine and pseudoephedrine, which successfully eliminated the artifact. The occurrence of the methamphetamine artifact was a rare, anal in many cases, irreproducible situation, but nonetheless of significant concern. Most laboratories use the periodate treatment for elimination of chromatographic interference of ephedrine OI pseudoephedrine rather than from fear of the artifact. With controls on the availability of large amounts of ephedrine and pseudoephedrine, the interference from these compounds is now quite rare.