Molecular characterization of sulfur-containing compounds in petroleum is of great significance for not only the oil refining but also geochemical application. One practical approach for the characterization is to convert nonpolar sulfur compounds into methyl sulfonium with methyl iodide/AgBF4 and to analyze them by electrospray ionization high-resolution mass spectrometry. However, the derivatization requires a very long reaction time, which limits the wide application of this method. In this study, we proposed a new derivatization reagent, silver hexafluoroantimonate (AgSbF6), which can significantly reduce the reaction time. The method was validated by model sulfur compounds and successfully applied on the crude oil and diesel fraction. A comparison between AgBF4 and AgSbF6 was conducted to evaluate the advantages of this method. The new reagent provides a high conversion yield and low structural discrimination and, thus, can be used to characterize a trace amount of refractory sulfur compounds in deep hydrodesulfurization fuels. In addition, a quick methylation can be more useful for selective separations of thiophenes and sulfides from petroleum fractions than the methylation/demethylation method.