Credit: CFSRE
From one end of the country to the other, officials are tracking yet another nitazene analogue that has caused at least 20 overdose deaths to date. Recently acquired in vitro pharmacological data shows this emergent novel synthetic opioid—called N-pyrrolidino protonitazene (also protonitazepyne)—is 25x more potent than fentanyl.
Nitazene analogues are a novel class of synthetic opioids that can be up to 40 times more potent than fentanyl and up to 500 times more potent than morphine. While they vary in potency, most retain opioid receptor activity.
In January, for example, the Center for Forensic Science Research & Education (CFSRE), identified N-Desethyl isotonitazene in samples from Pennsylvania and Florida. This nitazene analogue is up to 20x more potent than fentanyl. N-desethyl was first found in urine samples from a drug treatment program in Pennsylvania in September 2022. The synthetic opioid then quickly made its way south, showing up in counterfeit “A215” round blue tablets that were sold as oxycodone in Florida in November 2022.
Similarly, N-Pyrrolidino protonitazene was first reported by CFSRE’s NPS Discovery in January 2023, but the date of first sample collection was as early as December 2022. Now, as of August 2023, N-pyrrolidino protonitazene has been confirmed in 20 forensic toxicology cases, all of which were medicolegal death investigations.
The cases originated from 7 states across the continental U.S.: Maine (1), Massachusetts (1), Illinois (6), Wisconsin (3), Minnesota (1), Wyoming (3) and California (1). According to CFSRE’s data, there have also been four N-Pyrrolidino protonitazene overdose deaths in the U.K. In Australia, public health officials have reported protonitazene as a yellow powder being sold as ketamine.
In the analyzed samples, N-Pyrrolidino protonitazene was found in combination with:
- Additional novel psychoactive substances- 70%
- Quinine- 60%
- Other Nitazene analogues- 55%
- Methamphetamine/cocaine- 55%
- Fentanyl- 55%
- Xylazine (zombie drug)- 35%
- NPS benzodiazepines- 30%
“The toxicity of N-pyrrolidino protonitazene has not been examined or reported but recent association with overdoses among people who use drugs leads professionals to believe that this synthetic opioid has the potential to cause harm and is of high public health concern globally,” said the CFSRE in a recent public health alert.
In the field, FTIR and fentanyl test strips are not effective for detecting nitazene analogues. Naloxone should work to reverse a suspected overdose, although repeated administration may be necessary. Additionally, the condition of the patient could change rapidly and unpredictably after naloxone administration due to other drugs or precipitation of withdrawal, which may be more severe with faster onset.
In the forensic lab, non-targeted testing protocols should be used for synthetic opioids and novel drugs. Mass spectrometry-based screening is necessary, though in some cases, even GC-MS sensitivity may not be adequate.