Not all forensic toxicology laboratories are likely to detect these substances. Common toxicological analysis consists of a presumptive screening test (e.g. immunoassay) and a confirmatory test (e.g. gas chromatography/mass spectrometry or GCMS). In many laboratories, if the immunoassay screening test is negative then additional tests may not be performed. Enzyme-linked immunosorbent assay (ELISA) is a popular screening technique in forensic toxicology laboratories that perform human performance or postmortem investigations because of its heterogeneous nature, making it amenable to a wide variety of toxicological specimens with minimal sample preparation. Commercial ELISAs are widely available for amphetamine-type drugs including methamphetamine, amphetamine and MDMA. The methodology is well established and provides a reliable means by which a laboratory can presumptively identify positive samples for confirmatory testing.

The cross-reactivity of the assay towards other structurally related substances describes in quantitative terms, the ability of the antibody to bind to drugs other than the target analyte. Cross-reactivity is the result of poor antibody specificity. This lack of specificity can be exploited in a beneficial way to develop immunoassays that provide broad spectrum screening, for example when multiple drugs within a class are of interest (e.g. opiates, benzodiazepines). The immunogen structure largely defines antibody specificity. Large carrier proteins must be attached to small drugs to elicit an immune response, and this often results in poor specificity towards the region of the drug where the conjugation took place. For the amphetamine class, immunoassays generally employ antibodies of moderately high specificity (Suttijitpaisal and Ratanabanangkoon, 1992) for good reason. This approach minimizes unwanted cross-reactivity towards over-the-counter drugs (e.g. ephedrine, pseudoephedrine), putrefactive amines in postmortem samples, and other structurally related endogenous substances.

In the absence of immunoassay screening tests specifically directed towards the psychedelic amphetamines, the cross-reactivity of these compounds using commercial immunoassays used in forensic toxicology laboratories must be investigated. A low cross-reactivity towards these substances would indicate that reliance on ELISA, or other immunoassay-based screening methodology, may result in these abused substances not being detected in forensic case samples.

Reference: US Department of Justice: Designer Amphetamines in Forensic Toxicology Casework, 2013