Intoxications and Fatalities Associated with the Ingestion of the Novel Synthetic Cathinone, N-Isopropyl Butylone

Abstract Synthetic cathinones represent an expanding class of novel psychoactive substances (NPS), with their proliferation largely driven by international drug control measures and the rapid cycling of structural analogues designed to circumvent legislative scheduling. Following the international control of N,N-dimethylpentylone (DMP) in 2024, N-isopropyl butylone (NiPB) was increasingly detected in forensic toxicological casework as the prevalence of DMP declined. However, limited data currently exists regarding NiPB’s concentration ranges in forensic investigations. This report describes a validated liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS) method for the quantitation of NiPB in biological specimens, which was applied to the analysis of drugged driving (n = 1) and postmortem (n = 15) cases. The DUID case yielded a blood NiPB concentration of 16 ng/mL, whereas the remaining 15 cases demonstrated blood concentrations ranging <1 to 1400 ng/mL. For one case, NiPB was quantitated in blood, vitreous fluid, and urine, with concentrations of 18, 17, and 2200 ng/mL, respectively. Polydrug use was observed for all cases, and frequently included fentanyl (75%), traditional stimulants (63%), other synthetic cathinones (50%), ethanol (31%), and additional NPS such as bromazolam (19%) and MDMB-4en-PINACA (13%). Concentrations overlapped between antemortem and postmortem cases and were comparable to those reported for structurally related beta-keto methylenedioxyamphetamines, suggesting similar use scenarios and toxicological profiles shared across this analogue class. Although NiPB was identified as a contributing factor in several fatalities, the lack of pharmacological and toxicological data limits further interpretation of measured concentrations and the extent of its contribution to these fatal outcomes. Additional studies incorporating paired central and peripheral blood specimens are warranted to better characterize potential postmortem redistribution and its impact on NiPB blood concentration interpretation. Overall, this case series addresses a critical literature gap on NiPB by providing analytical and interpretive data to support forensic laboratories as NiPB identifications increase within the evolving NPS stimulant market.