Purity estimation of seized stimulant-type new psychoactive substances without reference standards by nitrogen chemiluminescence detection combined with GC-APCI-QTOFMS

•Reference standards for new psychoactive substances (NPS) are not readily available.•Nitrogen chemiluminescence detection (NCD) possesses equimolar response to nitrogen.•GC-NCD allowed purity estimation of stimulant NPS with only two external calibrators.•The grand mean equimolarity of twenty-eight stimulants studied was 91.9%.•This platform is potentially applicable to instant purity assessment of seized NPS. Purity assessment of seized material containing new psychoactive substances (NPS) is complicated without appropriate primary reference standards. Here we present a method for fast quantitative estimation of stimulant-type NPS with use of secondary reference standards, based on gas chromatography nitrogen chemiluminescence detection coupled with atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-NCD-APCI-QTOFMS). Quantification was based on the detector’s N-equimolar response to nitrogen and using two external nitrogen-containing calibrators, MDMA for prim- and sec-amines and α-PVP for tert-amines. Sample preparation involved dissolving the seized powdery material in an organic solvent mixture followed by acylation with N-methyl-bis-trifluoroacetamide (MBTFA). The method’s between-day accuracy and precision over a five-day period was measured for twenty-eight stimulants: the grand mean equimolarity was 91.9% (CV 5.5%), as compared with primary reference standards. The GC-NCD-APCI-QTOFMS method was applied to the purity estimation of forty-two seized powder samples previously found to contain stimulant-type NPS by appropriate methods. The quantitative results were compared to those obtained by an established method relying on liquid chromatography chemiluminescence detection (LC-CLND), the latter using caffeine as an external calibrator. The mean difference of purity values between the methods was 8.1% (range 0.4–26.7%). The presented method might find use as a tool for instant purity assessment in forensic laboratories.