Although immunoassays have the advantage of being relatively quick and inexpensive, they have one major challenge: cross-reactivity. Compounds other than the target drug can elicit a response in an immunoassay. This happens when a molecule is similar enough to the target drug to interact 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, a low occurrence of false positives is the immunoassay for cocaine. This test reacts quite precisely with the primary metabolite of cocaine, benzoylecgonine. There is a shallow occurrence of cross-reactivity with other compounds. Therefore, a positive result for benzoylecgonine is highly predictive of cocaine use. In this case, the antibody that binds and detects benzoylecgonine is particular to benzoylecgonine 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 that have similar structures, such as ephedrine, pseudoephedrine, and phenylpropanolamine (which can be present in over-the-counter cold and decongestant medications) can cross-react with some amphetamine immunoassays if they are present in high enough concentrations.
