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

Leukotrienes (LT) C 4 , E 4 and N ‐acetyl‐E 4 , their respective monomethyl esters and 14,15‐ 2 H 2 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 LTC 4 ) or lipid‐derived (predominant for LTE 4 ) moieties. More pronounced differences were observed between the fragmentations of [ M ‐ H] − ions derived from LTC 4 and LTE 4 ; 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 LTC 4 indicated a low‐picogram detection limit.