Selective N-pyridinium derivatization for molecular characterization of neutral oxygenated compounds in fossil fuels by high-resolution mass spectrometry.

Neutral oxygenated compounds (NOCs), including alcohols and ketones, constitute one of the most analytically challenging classes of molecules in the molecular characterization of fossil fuels, largely owing to the absence of selective analytical methods capable of detecting them at trace concentrations. Here, we report a selective chemical derivatization strategy using deuterated pyridine (D₅-pyridine) and thionyl chloride (SOCl2) to convert alcohols and ketones into N-alkylpyridinium quaternary ammonium salts. The resulting derivatives exhibit greatly enhanced ionization response in positive-ion electrospray high-resolution mass spectrometry (ESI(+) Orbitrap MS). Importantly, the use of D₅-pyridine eliminates spectral interference from native basic nitrogen compounds in crude oil, enabling unambiguous assignment of molecular formulas. The method allows simultaneous profiling of both alcohols and ketones with excellent selectivity, as confirmed by model compound studies. Quantification using 1-tetradecanol (C14-alcohol) and 3-tetradecanone (C14-ketone) as internal standards demonstrates good linearity (R2 > 0.96). Application to seven crude oils from Chinese oilfields reveals that alcohols (0.4~4.0% w/w) and ketones (0.015~0.070% w/w) are predominantly present as aliphatic, alicyclic, and aromatic structures, with oxygen levels below the detection limit of conventional elemental analyzers. This derivatization-based approach provides an analytical tool for tracing neutral oxygenated compounds in petroleum systems and demonstrates that these compounds contribute minimally to the total oxygen content of conventional fossil fuels compared to acidic oxygen-containing species.