A 112-μg sample of DNA was spiked with 103 pg of N 7-(2′-hydroxyethyl)guanine and 100 pg of N 7-(2′-hydroxyethyl-d4)guanine, the internal standard. The sample was subjected to the following sequence of steps: heating at 100°C, precipitation of the DNA with HCl, reaction with nitrous acid to form the corresponding xanthines, reaction twice with pentafluorobenzyl bromide (first to derivatize NH, then OH), solid-phase extraction on silica and detection by gas chromatography-electron capture mass spectrometry. The absolute, overall yield of final product for both the analyte and internal standard was 9.7%. Conveniently, the three chemical reactions are conducted sequentially in the same vial and, aside from a washing step, are separated only by evaporations. Corresponding N 7-guanine methyl, phenyl and styrene oxide adducts were detected at about the 50-ng level by the procedure, to indicate the generality of the method.