By Rebecca Wood
Nitazenes are a group of highly potent synthetic opioids belonging to the 2-benzylbenzimidazole class that began to emerge in toxicology casework around 2019 after their original development in the 1950s. Since then, they have become an increasing concern in the field of toxicology due to their extreme potency and involvement in fatal overdoses.
I started working in post-mortem toxicology in 2023, at a time when nitazenes had shifted from being detected very occasionally in our casework to appearing every couple of weeks. As with many emerging drugs, this raised questions not just about prevalence, but about how reliably we were detecting them.
On two separate occasions, due to a backlog at the mortuary, we received a sample for toxicology before the post-mortem examination had taken place, followed by a second sample collected approximately a week later during the post-mortem. In both cases, nitazenes were detected in the initial sample. However, when we went to confirm these findings in the later post-mortem sample, the nitazenes had vanished.
This immediately raised an important question: had we done something wrong analytically, or was something happening to these compounds during the post-mortem interval?
Through collaboration, we were able to formally investigate nitazene stability both in vivo (within the body) and in vitro (within the collected sample). Using a rat model, animals were administered a dose of a nitazene, with blood samples collected at day 0. The animals were then stored in the fridge and further samples were collected on day 7. Both the day 0 and the day 7 samples were analysed and then were refrigerated and reanalysed one month later.
The results of this work, published in early February 2026, showed that nitazene concentrations decrease over a seven-day post-mortem interval. In addition, concentrations also declined within stored samples over time, even when refrigerated. Importantly, this was noted in both unpreserved and fluoride oxalate preserved samples. Fluoride oxalate is used in post-mortem toxicology to inhibit enzyme activity and prevent degradation of compounds within samples, however, this did not seem to preserve nitazenes either.
This leads to an uncomfortable but important question: if nitazenes are unstable both within the body after death and in collected samples, how many cases have we missed? How many deaths may have involved nitazenes that were never detected simply because the drug had degraded before analysis?
These are questions that are impossible to answer. As a result, the true extent of harm caused by this class of drugs may never be fully understood. This under-detection has wider consequences, affecting drug trend monitoring and, in turn, our ability to develop timely and effective public health responses to this threat.
This instability also has important implications for how toxicology results are interpreted. Just because a nitazene is not detected does not mean it was not present at the time of death. This complicates how toxicology findings are used when determining cause of death and highlights the risk of over-interpreting negative results in cases where there is a strong suspicion of opioid involvement.
More broadly, this work highlights a wider issue with novel psychoactive substances. New compounds can emerge rapidly, often with little or no data on their post-mortem stability. Toxicology testing is therefore always playing catch-up, and even when analytical methods are capable of detecting a substance, instability during the post-mortem interval or sample storage can still lead to false negatives.
Ultimately, nitazenes may not be unique in this regard. Their instability serves as a warning that other emerging drugs may also be disappearing before they are ever detected. As the illicit drug market continues to evolve, it is essential that toxicology, pathology, and public health systems adapt alongside it. Recognising the limitations of our testing, prioritising early sample collection and analysis, and continuing to investigate the stability of new substances will be critical if we are to avoid underestimating the true scale of drug-related harm.
Reference:
https://www.tandfonline.com/doi/full/10.1080/15563650.2025.2601141
