Helping you stay current in drug monitoring

Presumptive and definitive testing: make the right choice by understanding the differences

Presumptive, definitive, qualitative, quantitative, immunoassay, mass spectrometry, point-of-care: there is a lot of terminology to get right when it comes to drug testing. Understanding the terminology is critical for making the right testing choice for your patient. In a recent podcast, Drs Jeff Gudin and Jack Kain outlined the key differences among different types of tests and provided advice on how to choose the one best suited to your needs.

The most important distinction in testing is between presumptive and definitive testing, according to Dr. Gudin. They differ in the methodology, but even more important, in what information they can, and can’t, provide.

“A presumptive test is often used as an initial drug screen and can be done either in the lab or on-site with a point-of-care test,” Dr. Gudin said. Presumptive tests typically use an immunoassay, in which an antibody binds to the substance of interest and suggests drug positivity.

The benefit of a presumptive test is that it can screen a large number of analytes at once, potentially finding the proverbial needle in a haystack, and can do so quickly. “Unfortunately, immunoassays will detect substances with similar characteristics, resulting in cross-reactivity leading to false-positive results,” Dr. Gudin said.

This is because the antibody binding that is at the heart of the test depends on shape and charge, which may be shared by several different molecules in the sample. Ibuprofen and marijuana cross-react, for instance. “False positives cannot be distinguished from true positive results in the presumptive test,” Dr. Gudin noted, and the test cannot provide definitive identification of which drugs or drug metabolites are present.

A definitive test uses different methodology and identifies the specific molecules in the sample. “Definitive assays rule out false-positive results and identify true-positive drugs or drug metabolites,” Dr. Gudin said.

Modern definitive tests use gas or liquid chromatography to separate analytes, followed by mass spectrometry to identify them based on their unique mass. “This is the gold standard for identification,” he said.

In the past, “qualitative” and “quantitative” were used to refer to tests that today are called “presumptive” and “definitive,” respectively. That earlier usage is now obsolete. Today, a presumptive test result is always reported qualitatively, as either “negative” or “presumptive positive.” Results from a definitive test may be reported either qualitatively (negative or positive for the tested drug/metabolite) or quantitatively (with quantitation of drugs/metabolites).

So how should a physician choose which test to use? There is no one-size-fits-all answer, Dr. Kane said, however, there are a couple of key considerations to keep in mind. If a presumptive test returns a negative result, testing can end at that point, since the negative result indicates that no substance of interest was found. If the result is positive, only a definitive test can determine whether the result is a true positive or a false positive. And if quantification is needed, only a definitive test can provide that.

Consensus recommendations from the American Academy of Pain Medicine for patients receiving prescribed opioids indicate that definitive testing is most appropriate for urine drug monitoring, because of its accuracy, but that presumptive testing may be required by institutional or payer policies.

“In every case, the rational choice of substances to analyze for urine drug monitoring is patient-specific,” Dr. Gudin noted, based in part on illicit drug availability. AAPM guidelines note that the frequency of monitoring is also patient-specific, based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous monitoring results.