Fatalities caused by novel opioids: a review

Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic. Most of these are based on fentanyl structures that are much more potent, and dangerous, than fentanyl itself. This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids. These drugs include reports of deaths to acetylfentanyl, acrylfentanyl, butr(yl)fentanyl, carfentanil, 2- and 4-fluorofentanyls, 4-fluorobutyrfentanyl, 4-fluoroisobutyrfentanyl, furanylfentanyl, alpha- and 3-methylfentanyls, 4-methoxyfentanyl, ocfentanil, as well as AH-7921, U-47700 and MT-45. Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid. No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided, however, the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures, particularly when screening specimens using a non-targeted mode. Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl, cyclopentylfentanyl and tetrahydrofuranfentanyl, all of which are likely to have the potential to cause death. It is also likely that other analogues will appear with time.