By Kevin Shanks, M.S., D-ABFT-FT
As we have discussed on this blog several times in the past, novel psychoactive substances (NPS) come in different varieties, which include cannabinoids, stimulants, opioids, benzodiazepines, and hallucinogens. One of Axis Forensic Toxicology’s objectives it to be able to detect the most recently emerged NPS on the street in a timely manner. With that said, a new fentanyl derivative has emerged!
Chemical Structure of ortho-Methylfentanyl Drawn by Kevin G. Shanks (2025)
Ortho-Methylfentanyl is a fentanyl analog or derivative that has emerged in the United States as an NPS in both powders and counterfeit tablets. It has a chemical formula C23H30N2O and a molecular weight equal to 350.5 g/mol. It is structurally-related to fentanyl with the fundamental difference in chemical structure being in the position of a single methyl (-CH3) group, which is attached to the ortho- position of the phenyl ring. There are two other positional isomers: meta- and para-methylfentanyl. The ortho isomer of methylfentanyl was first detected in 2023 in British Columbia, Canada, but over the last two years, it was been detected across Canada and the United States. In the United States, the substance is considered a Schedule I controlled substance and is illegal to synthesize, possess, and distribute.
Pharmacologically, it is a mu (µ) opioid receptor agonist, much like morphine, oxycodone, and fentanyl. It also shares a similar analgesic potency with fentanyl. As a mu opioid receptor agonist, the effects of the substance would include analgesia, tiredness, drowsiness, sedation, and in overdose, severe respiratory depression, hypoxia, apnea, coma, and potentially, death.
In early 2025, we first detected ortho-methylfentanyl in our postmortem toxicology sample population and have now added it to our Designer Opioids panel (order code 13810) and the Comprehensive Panel, Blood with Analyte Assurance™ (order code 70510) using liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS). Reporting limit is 50 pg/mL.
Axis also has the ability to monitor other novel opioids to include acetylfentanyl, acrylfentanyl, AP-237, AP-238, betahydroxythiofentanil, brorphine, carfentanil, cis-3-methylfentanyl, cyclopropylfentanyl, furanylfentanyl, isobutrylfentanyl, methoxyacetylfentanyl, ocfentanil, para-fluorobutyrylfentanyl, para-fluoroisobutyrylfentanyl, tetrahydrofuranfentanyl, tianeptine, U-47700, and valerylfentanyl.
As always, if you have questions about ortho-methylfentanyl and how it (or any other novel emerging compound) may play a role in your medical-legal investigation, please reach out to our subject matter experts by email ([email protected]) or phone (317-759-4869, Option 3).
Stay tuned to this blog for more quick drug primers on more novel compounds we have recently added to our testing scope!