Tetramethylammonium hydroxide as a reagent for complex mixture analysis by negative ion electrospray ionization mass spectrometry.

Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) enables the direct characterization of complex mixtures without prior fractionation. High mass resolution can distinguish peaks separated by as little as 1.1 mDa), and high mass accuracy enables assignment of elemental compositions in mixtures that contain tens of thousands of individual components (crude oil). Negative electrospray ionization (ESI) is particularly useful for the speciation of the most acidic petroleum components that are implicated in oil production and processing problems. Here, we replace conventional ammonium hydroxide by tetramethylammonium hydroxide (TMAH, a much stronger base, with higher solubility in toluene) to more uniformly deprotonate acidic components of complex mixtures by negative ESI FTICR MS. The detailed compositional analysis of four crude oils (light to heavy, from different geographical locations) reveals that TMAH reagent accesses 1.5-6 times as many elemental compositions, spanning a much wider range of chemical classes than does NH4OH. For example, TMAH reagent produces abundant negative electrosprayed ions from less acidic and neutral species that are in low abundance or absent with NH4OH reagent. More importantly, the increased compositional coverage of TMAH-modified solvent systems maintains, or even surpasses, the compositional information for the most acidic species. The method is not limited to petroleum-derived materials and could be applied to the analysis of dissolved organic matter, coal, lipids, and other naturally occurring compositionally complex organic mixtures.