Although immunoassays have the advantage of being relatively quick and inexpensive, they have one major challenge: cross-reactivity. It is possible for compounds other than the target drug to elicit a response in an immunoassay. This happens when a molecule is similar enough to the target drug that it interacts with the detection or capture antibody. This is referred to as cross reactivity.
An example of a test with a low occurrence of cross-reactivity and therefore, low occurrence of false positives, is the immunoassay for cocaine. This test reacts quite specifically with the primary metabolite of cocaine, benzoylecognine. There is very low occurrence of cross-reactivity with other compounds. Therefore, a positive result for benzoylecognine is highly predictive of cocaine use. In this case, the antibody that binds and detects benzoylecognine is very specific to benzoylegonine and does not bind to other common drugs, metabolites or compounds, that may be present in the sample.
On the other hand, immunoassays for amphetamine and methamphetamine are notorious for having high cross reactivity and thus, a high occurrence of false positives. Other sympathomimetic amines which have similar structures, such as ephedrine, pseudoephedrine, and phenylpropanolamine which may be present in over-the-counter cold and decongestant medications, are commonly known to cross-react with amphetamine assays.
