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The page below is a sample from the LabCE course Drug Testing Methods in the Clinical Toxicology Laboratory. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Immunoassay Techniques: Cross-Reactivity

Although EIAs have the advantage of being comparatively quick and inexpensive, they do have one major challenge, cross-reactivity. It is possible for compounds other than the target analytes to elicit a response in an immunoassay if they are similar in structure to a drug, metabolite, or class of drug. 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 test for cocaine. This test reacts 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.
On the other hand, the EIA for amphetamine and methamphetamine suffer from high cross-reactivity and 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.