A metabolite is defined as “a substance produced during metabolism, which is the process of digestion and other bodily chemical processes”. Essentially anything you put into your body is metabolized in one way or another. Food, for example, metabolizes into vitamins, proteins, fats, sugars, etc. Some food metabolites are useful chemicals your body needs, and some are discarded and excreted as waste byproducts.

Just like food, some substance metabolites are used by your body for various functions, and some are discarded and excreted as waste byproducts. In almost all cases, the process does not metabolize 100% of whatever was ingested, and to varying degrees is excreted unchanged from what was ingested (we call this the “parent compound”). A good common example of this is when you take too much Vitamin C, some of it is excreted unchanged; this is why we sometimes see bright orange urine when we take Vitamin C.

So why does this matter to us regarding drug testing? Since both the parent and the metabolite compounds are present in urine, it is important for a drug test to detect both. Moreover, the metabolites are detectable in urine much longer than their parents. Because of the longer window of detection, virtually all screens for drugs of abuse use metabolites as their target substance; this target substance is also known as the calibrator. When we talk about the cut-off level of a test, we are referring to the concentration at which the calibrator substance (again, typically the metabolite) will trigger a positive result.

While extremely oversimplified, the chart below gives us an idea of how parents and metabolites are excreted via urine. We can see at the far-left side of our timeline (we’ll call that the “onset” of the window of detection), the level of parent substance being excreted is much higher than the metabolite. Then about halfway through our timeline, we see equal amounts of parent and metabolite. Lastly, toward the “outset” of our window of detection we can still detect the metabolite, but the parent has fallen below the concentration needed for detection. So, for example, when testing for Fentanyl we will be able to detect Norfentanyl – its metabolite – for a much longer period of time after use than the parent Fentanyl.

While instant urine tests for drugs of abuse have improved tremendously over the years, the simple fact that it is still just a method of screening tells us that there are some limitations in the amount of information that they provide. Here we will discuss some of the obvious (and less obvious) reasons why laboratory confirmations should be considered a crucial part of your testing program.

First and foremost, it is part of the manufacturers’ instructions for use; usually worded to the effect of “This assay provides only a preliminary analytical test result. A more specific alternate methodology must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) are the preferred confirmatory methods”. If I provided no additional reasons beyond this, that it is listed as a “must” in the instructions is a pretty compelling argument.

Let’s discuss some of the reasons that test manufacturers (and the FDA, whose guidance compels these instructions) find this so important…

Firstly, it is no secret that drugs screens – whether an instant device, or a “desktop analyzer” type device – are not 100% accurate. While most panels on our instant tests are greater than 99% accurate, it is this remaining 1% that needs to be accounted for. A good example of this is known cross-reacting substances; using the Fentanyl panel as our example, we know that the medication Buspirone (Buspar) can cause a false positive on the Fentanyl panel. The only way to be sure that the positive result is due solely to the Buspirone would be to have the specimen confirmed via laboratory. There are no cross-reactions on a laboratory confirmation.

Another reason lab confirmations are crucial is the fact that most of the panels on an instant test react with many substances within that drug class. An example I like to use for this instance would be the Benzodiazepine (BZO) panel. Let’s say you have an individual who is prescribed Alprazolam (Xanax), but maybe you have suspicions of other Benzos being used. You would expect to see a positive BZO due to the Xanax, but only a lab confirmation could determine if the positive was from the prescribed BZO, or a different BZO that may have been taken illicitly.

Levels in urine tests don’t provide much (if any) useful information, with one exception: checking for THC level over time. Of course, all instant screens are qualitative (positive or negative) and cannot provide a quantitative result (level). In this instance, with the lab confirmation providing the quantitative result, you are able to check for THC level over time to monitor continued abstinence.

Lastly, I’m sure you have encountered outright denial of use, at least on a couple of occasions; something to the effect of “that can’t be right”, or “your tests are broken”, where they are hoping by some miracle the lab result will confirm their story. Of course, some will admit use after the results of the instant test, reducing the importance of confirming. The other side of the coin here is someone admitting use where nothing shows on the instant. In these instances, the lab will confirm at a lower cut-off level, and will typically show that the concentration of substance was just not high enough to react on the instant.

In summary, while the use of instant tests is a hugely beneficial tool, it can’t always tell the whole story. They do reduce the lost time and cost of having to send every specimen out, but do not completely preclude the need for laboratory testing.