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.

If you’ve watched our “Understanding the Limitations of Drug Testing” webinar or have had conversations with me about that subject, you’ve heard me talk about substances that many people expect to be detected on the tests that they are using, but actually are not.  An excellent example of this that we are all hopefully familiar with is Fentanyl. This synthetic opioid, for a long time, was expected to be detected on an Opiate panel but in fact it is not. As Fentanyl became more problematic, we increased our efforts to ensure that we were giving our customers the knowledge and the tools needed to test for this dangerous substance. Today we will discuss Hydrocodone and Clonazepam. While not nearly as prevalent as Fentanyl, these are two commonly prescribed drugs that do have the potential for abuse and are worth knowing about.

Hydrocodone is an Opioid pain medication, with Vicodin being the most prominent brand name. If you’ve ever had any serious dental work, you have probably heard of this one. Since it is an Opioid, it has a high potential for misuse and addiction, so it is a substance that is important to test for. However, the misconception is that this substance would be detected on the standard Opiate panel, or at least the Oxycodone panel.  Because these substances share a similar molecular structure, there is a possibility that Hydrocodone could be detected on either of those panels. However, the concentration of Hydrocodone in the specimen would have to be much higher than the other substances being detected, and therefore neither of those panels will ever be reliable tools for detecting Hydrocodone. Fortunately, we do have a Hydrocodone specific test, both as separate single-panel dip tests, and also included in select multi-panel cup configurations.

Clonazepam is a Benzodiazepine commonly known by the brand name Klonopin. Benzodiazepines, or Benzos, also have a high potential for misuse and addiction and is also an important substance to test for. Also, like Hydrocodone, it is possible that Clonazepam will trigger a positive on the standard Benzodiazepine panel, but it will not be at all reliable. The Benzodiazepine panel was designed to detect the most common Benzodiazepines. So, a standard test will detect about 20 of the 50+ Benzodiazepines that exist in the world, but Clonazepam is different enough in both molecular structure, and in the way the human body metabolizes it, that it will not be reliably detected. For this reason, such as with Hydrocodone, we do offer a Clonazepam specific test in both a single-panel dip test, and as part of select multi-panel cup configurations.

The big takeaway here is that it is important to know what substances will be detected on the panels you are testing with. While the tests are engineered to detect as many drugs in a specific class as possible, sometimes differences in chemistry and biology make this impossible. Fortunately, in almost all cases, we have the tool available that will fill these “blind spots”.

As always, for additional information or discussion on this topic, please reach out to me or your consultant.

Today’s subject was sparked from a conversation that our sales consultants have fairly regularly. Usually this comes up in the context of us pressing to find out why a facility is using the specific tests that they are using. The answer we get more than any other is some variant of, “it’s just the way we’ve always done it.” If you’ve had any conversations with our sales team, you know they won’t simply let that answer stand alone. It is always our mission to understand the needs of each facility we work with, but sometimes this can entail explaining why some of the thought processes behind those needs might be misguided, outdated, or missing crucial bits of information.

For example, when inquiring why a facility is not testing for Fentanyl, when it is clearly the most concerning drug of abuse, we will often hear the previously mentioned, “it’s just the way we’ve always done it”, or, specific to Fentanyl, “we assumed that this would be detected on our Opiate panel”. This covers all three of the thought processes I described.

However, for this blog post, we are going to focus on the other side of this coin, substances that people have been testing for that may or may not be necessary. Keep in mind, I will never fault anyone for playing it safe and testing for everything that they can, but this doesn’t always work for facilities that need to keep costs down. I always recommend that people find a happy medium, and keeping our clients informed about substances that are of the highest concern at the time is incredibly important in helping such facilities try and find that happy medium.

Today we are going to look at Propoxyphene (PPX) and Tricyclic Antidepressants (TCA) with a nod to a couple of honorable mentions in Barbiturates (BAR) and Phencyclidine (PCP).

First, Propoxyphene, more commonly known by its brand names, Darvon and Darvocet, is a mild Opioid pain reliever. It dates back to 1954 and was developed, like most Opioids, as an attempt to create a non-addictive pain medication. Spoiler alert, it was still addictive! Being that it was a mild Opioid, it did have a slightly lower risk of addiction, but it was neither non-addictive nor totally safe, as such, this medication has been taken off the shelves in the US since 2010. Most other First World countries follow suit shortly thereafter. While it is still prescribed in other countries, albeit infrequently, it is not completely gone from the world. However, with many more commonly prescribed, and therefore more readily available Opioids, I have never in my 20+ years heard of a Propoxyphene positive result, nor any facilities having concerns with its misuse.

Next up is Tricyclic Antidepressants. Tricyclic Antidepressants are a class of antidepressants characterized by their chemical structure, which contains three rings of atoms. TCAs were also developed in the early 1950s during the early days of psychopharmacology (psychopharmacology being medications to treat mental disorders). TCAs are typically classified as, “mood elevators”, and the most commonly known is probably Elavil (Amitriptyline). These medications have not been pulled from shelves like Propoxyphene, but they are rarely prescribed these days in favor of the more modern class of antidepressants, such as SSRIs (Prozac and Celexa), SNRIs (Cymbalta and Effexor), and NRIs (Wellbutrin). Near obscurity aside, according to the US government classification of psychiatric medications, “TCAs are non-abusable”. While in slightly higher demand than testing for Propoxyphene, TCAs can be a good place to cut back on if you are trying to keep costs down.

Honorable mentions: Barbiturates (BAR) and Phencyclidine (PCP).

Please do not interpret this as my advising not to bother, or that you don’t need to test for these, but I wanted to include this in an attempt to point out how uncommon these substances have become in terms of drugs of abuse. Barbiturates have long since been replaced in most cases with Benzodiazepines (especially for sedation). However, we do see a small number of prescription medications that contain them. Fioricet, for example, is a common medication prescribed for migraines.

If you are testing BAR, I am going to guess that you probably have never seen a positive result. To a lesser extent than BAR is PCP. This dissociative anesthetic was used medically from 1956 to 1965 (1978 for veterinary medicine), until discontinued due to high rates of negative side effects. We typically see the better tolerated, Ketamine (KET), being used for anesthetic purposes in its place. While we do sometimes hear about geographic pockets of the country where this substance pops up from time to time, it is not nearly as widespread as it once was.

In summary, do not take this article as the final word on what tests are best for you or your facility to use, but take this to open up a conversation about whether or not, what you are testing for is really what you need to test for, or if it is just the way you’ve always done things.