Preparation and tandem mass spectrometric analyses of deuterium-labeled cysteine-containing leukotrienes.

Leukotrienes (LT) C4, E4 and N-acetyl-E4, their respective monomethyl esters and 14,15-2H2 analogs have been synthesized. The collisionally activated decompositions of the [M + H]+ and [M - H]- ions formed by fast atom bombardment (FAB) have been studied by tandem mass spectrometry using a hybrid sector/quadrupole instrument. Structurally informative product ion spectra were obtained for each analyte; the fragmentation pathways proposed are consistent with the parallel data obtained for labeled and derivatized species. Fragmentation of [M + H]+ ions occurs prominently via cleavage of the thioether linkage with charge retention on the cysteine-containing (predominant for LTC4) or lipid-derived (predominant for LTE4) moieties. More pronounced differences were observed between the fragmentations of [M - H]- ions derived from LTC4 and LTE4; the preference for charge retention, however, parallels that observed for the fragmentation of [M + H]+ ions. Selected ion monitoring during continuous-flow FAB mass spectrometric analysis of authentic LTC4 indicated a low-picogram detection limit.