Ketones in fossil materials are a group of reactive compounds that may take part in reactions leading to the material becoming instable. Since they have never been much studied, we devised an analytical method based on high-resolution mass spectrometry. Two commercial reagents are compared as derivatization reagents to selectively introduce a positive charge into the ketones for the detection. The reagents are Girard T and a quarternary aminoxy (QAO) compound, and their suitability was tested in the analysis of ketones in a Wilmington crude oil. Orbitrap spectra were recorded to obtain high sensitivity and mass resolution. The derivatives had to be separated from basic nitrogen heterocycles through a simple and rapid chromatographic step to avoid complete suppression of the signals of the derivatives. QAO was superior to Girard T since a better detectability and a larger number of ketone signals were found. As a second complex real-world sample, a coal tar was investigated. Like in the crude oil, the ketones belonged to different classes of compounds: n-alkanones and saturated one- or two-ring structures, ketones containing aromatic rings, and ketones with either one additional oxygen or a nitrogen atom. Unique to the coal tar was a series of aromatic ketones with double bond equivalents up to 23, suggesting large aromatic structures, and with only a few (<= 4) carbon atoms in the side chains, while the corresponding ketones in the crude oil showed double bond equivalents up to 14 and a large number of carbon atoms in the side chains.