First confirmation of synthetic cathinone N,N-dimethylpentylone in postmortem sample in New Zealand using GC-MS/MS

Abstract

To develop a qualitative method for identifying N,N-dimethylpentylone in biological samples (blood and urine) using GC-MS/MS. This method has now been used to confirm the presence of N,N-dimethylpentylone in a coronial case for the first time in New Zealand. N,N-dimethypentylone (also known as dipentylone and dimethylpentylone) is a substituted cathinone derivative with stimulant effects. This designer drug was first detected in Sweden in 2014. N,N-dimethylpentylone can be metabolised into pentylone, which is an illegal substance in New Zealand and many other jurisdictions. Reports issued by the New Zealand and USA drug control agencies (New Zealand's High Alert, CFSRE, NPS discovery) have warned the public of the negative harm profile of N,N-dimethylpentylone. They also noticed the rapid replacement of eutylone by N,N-dimethylpentylone in the synthetic stimulate market and forecast an increase in the use of this substance in New Zealand. ESR Forensic Toxicology laboratory received the first N,N-dimethylpentylone sample from NZ drug control agents at the end of 2021. This sample was analysed initially on LC-MS/QTOF. However, due to the metabolization of N,N-dimethylpentylone and its close retention time with pentylone, our routine QTOF screening method was unable to distinguish these two compounds efficiently. GC–MS/MS has previously been used for the analysis of synthetic cathinone qualitatively and quantitatively by forensic research organisations. GC–MS/MS has proved to be a very powerful tool to separating different regioisomers from each other. In this study, we developed a qualitative method to distinguish N,N-dimethylpentylone and its metabolite pentylone in blood and urine using GC–MS/MS. An effective liquid-liquid extraction method was used to prepare blood and urine samples before injection into the GC–MS/MS. For the first time in New Zealand, we identified the presence of N,N-dimethylpentylone in one coronial urine sample. GC–MS/MS analysis. GC–MS/MS was performed using a Shimadzu GCMS-QP2010 system with ADC 6000 series autosampler, 10 μL injection needle, split mode with HP-5MS column (30 m × 0.25 mm i.d., 0.25 μm film thickness) at a constant flow (1 mL/min of helium). The GC-MS/MS operating parameters were as follows: inlet temperature set at 260 °C, interface temperature set at 280 °C, MS source set at 230 °C and EI and ionization energy under 70 eV. The analytes were monitored both in scan and selective ion monitoring (SIM) mode. The program governing GC temperature began with an initial temperature of 140 °C, where it was held for 2 min before being ramped up as follows: 140–180 °C at 50 °C/min, 180–195 °C at 5 °C/min, 195–220 °C at 10 °C/min and 220–280 °C at 50 °C/min. The final temperature was held for 2 min. The total run time was 12 min. The retention time and monitored ion of N,N-dimethylpentylone and pentylone was achieved by running the standard of these two compounds in scan mode on GC-MS/MS. Compound RT (min) Monitored ions: N,N-Dimethylpentylone 6.899 100, 58,149 and pentylone 6.619 86,121,65. The calibration curve used in this study was 0.05–0.25 mg/L. N,N-dimethylpentylone was detected in the urine exhibit of one coronial case, but not confirmed in the blood exhibit. We successfully developed a method to detect N,N-dimethylpentylone and its metabolite pentylone using GC-MS/MS. Our future work will focus on validating this method and analysing more samples. We expect to be able to provide more information about the overall use of N,N-dimethylpentylone in New Zealand and give more support to our drug control agencies.