Orbitrap mass spectrometry as a new platform for stable isotope forensics: A case study of sarin gas precursors

The abundances of stable isotopes in a compound are a valuable forensic tool because they provide a fingerprint which can determine that compound’s source substrates, synthetic route, and degradation mechanisms. For example, suppose a compound’s initial carbon feedstock comes from methanol, via two synthetic routes: route A results in enrichment of ¹³C relative to the source, while route B causes no change in ¹³C content. In this case, by comparing an isotopic measurement of ¹³C to known methanol sources, investigators may be able to distinguish between synthetic routes. In order to make full use of isotopic information, measurements of multiple elements and position-specific isotopic content (e.g., the amount of ¹³C at a carboxyl carbon vs a methyl carbon) must be combined. Recent developments in Orbitrap isotope ratio mass spectrometry (Orbitrap-IRMS) have made such measurements more practical, making it a powerful tool for chemical forensics. I will discuss this progress and present a case study of forensic application to the sarin gas precursor methyl phosphonic dichloride (DC). In this experiment, we first hydrolyze DC to methylphosphonic acid (MPA), which preserves the isotopic content of the methyl group; a subsequent Orbitrap-IRMS measurement simultaneously characterizes the carbon and hydrogen isotopes of this methyl group at high precision (δ¹³C ≈ 0.9 ‰; δ²H ≈ 3.6 ‰). This methodology is applicable to small sample sizes, consuming ≈60 nmol of analyte. I’ll close by describing the prospects of this new technique for future forensic measurements.