Laboratory‑Confirmation Drug Testing: Modern Challenges & Extensions
In modern workplace settings, initial non-negative rapid immunoassay or screening tests are typically followed by confirmatory analyses—usually based on chromatographic separation plus mass spectrometric detection. (GC/MS or LC/MS) Confirmation is essential to avoid false positives, exclude cross‑reactivity, and also provides quantitative results usable in legal employment decisions.
Key updates in laboratory drug testing for 2025
As drug use trends change, laboratories need to update how they confirm and interpret test results. In 2025, three areas have become especially important:
- Cannabinoids (with the rise of Δ⁸-THC)
- Benzodiazepines (with more focus on alprazolam / known by brand name Xanax is US)
- Ketamine (by including its main metabolite, norketamine)
These changes ensure that results are accurate, legally defensible, and better reflect what people are actually using.
Cannabinoids: Moving Beyond Δ⁹-THC
Traditionally, cannabis testing has focused on Δ⁹-THC (Delta-9 Tetrahydrocannabinol), the main psychoactive compound in cannabis, and its long-lasting breakdown product Δ⁹-THC-COOH (11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol). This metabolite is what most urine tests pick up.
However, Δ⁸-THC (Delta-8 Tetrahydrocannabinol) is now widely available in edibles, vapes, tinctures, gummies, and drinks—often marketed as “hemp-derived.” It produces similar but slightly weaker effects compared to Δ⁹-THC (around 50–70% of the psychoactive strength) because it still binds to the CB1 receptors (cannabinoid receptors in the brain responsible for the “high”).
Because Δ⁸-THC is almost chemically identical to Δ⁹-THC, it breaks down into a similar metabolite called Δ⁸-THC-COOH. This creates two major challenges:
- Cross-reactivity in screening tests – Standard immunoassays (broad screening tests used in workplace or clinical settings) may mistake Δ⁸ metabolites for Δ⁹, leading to false positives or misleading results.
- Separation in confirmatory tests – Since Δ⁸ and Δ⁹ are isomers (same chemical formula but slightly different structure), labs need high-precision techniques such as LC-MS/MS (Liquid Chromatography with Tandem Mass Spectrometry) or GC-MS (Gas Chromatography with Mass Spectrometry) to tell them apart.
Studies show that in certain testing populations, around 12–14% of samples contain Δ⁸-THC metabolites. That’s too common to ignore.
Best practice now means: use confirmatory methods that clearly separate Δ⁸ from Δ⁹, report which isomer was detected (not just “THC”), and regularly review prevalence data to decide whether Δ⁸ testing should be routine.
Benzodiazepines: Including Alprazolam (Xanax)
BZDs (Benzodiazepines) are prescribed for anxiety, insomnia, and seizures. Examples include diazepam (Valium), and lorazepam (Ativan). While alprazolam (Xanax) is not currently available on NHS prescription, private and illicit use appears to be growing. Aprazolam is widely misused in the US and in other countries.
Most screening tests only show whether some benzodiazepine is present, but they may miss certain drugs. That’s why confirmatory testing (using LC-MS/MS or GC-MS) is essential—it can identify exactly which drug and metabolites are in the sample.
Why alprazolam matters:
- It’s short-acting and one of the most commonly globally misused benzodiazepines.
- Its main metabolites, α-hydroxyalprazolam and 4-hydroxyalprazolam, may be the only detectable markers in urine once the parent drug has been broken down.
- Some immunoassays don’t pick it up reliably.
Best practice now means: always include alprazolam and its metabolites in standard BZD confirmation panels, use internal standards (reference compounds added during testing to improve accuracy), and clearly report whether the parent drug, metabolite, or both were detected.
Ketamine: Adding Norketamine
Ketamine is used both in medicine (as an anaesthetic or for mental health treatment) and recreationally. In the body, it’s rapidly broken down into norketamine (its main metabolite, which is still active and lasts longer), and sometimes further into dehydronorketamine (another breakdown product).
If labs only test for ketamine itself, they may miss exposure—especially if the test happens hours after use. By including norketamine in confirmatory testing, labs can extend the detection window, strengthen evidence of real use, and help estimate timing of use.
Best practice now means: confirm both ketamine and norketamine in urine or plasma using LC-MS/MS or GC-MS, report results with clear interpretation if only one is detected, and use isotope-labelled internal standards to guarantee legally defensible accuracy.
Key points to remember
Lab drug testing is evolving to keep pace with new patterns of drug use.
- Cannabinoids: Δ⁸-THC is now common enough that confirmatory lab drug testing should always separate it from Δ⁹.
- Benzodiazepines: Alprazolam (Xanax) misuse is increasing, so it must be included in drug test.
- Ketamine: Adding norketamine improves both sensitivity and interpretation on lab drug test results.
Why these updates matter
By refining how lab drug tests to detect these cannabinoids, benzodiazepines, and ketamine, laboratories can:
- Provide more reliable workplace drug testing
- Improve accuracy in clinical and forensic toxicology
- Keep results defensible in legal and compliance cases
These updates give more robust, reliable results and ensure UK drug testing laboratories can keep up with changing drug trends in 2025 and beyond.