Electrospray ionization and tandem mass spectrometry of cysteinyl eicosanoids:: Leukotriene C4 and FOG7

The cysteinyl leukotrienes, LTC4, LTD4 and LTE4, and the recently described cysteinyl eicosanoid, 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG,) have been analyzed by tandem mass spectrometry. Both [M-H](-) and [M+H](+) ions were produced by electrospray ionization and collision-induced dissociation of these molecular ion species were studied using both an ion trap and a triple quadrupole instrument. Product ion spectra obtained were characteristic of the structure of the cysteinyl leukotrienes and mechanisms of ion formation were investigated by using deuterium-labeled analogs. The product ion spectrum obtained following collision-induced dissociation of the [M-H](-) anion from FOG(7) was devoid of significant structural information and further studies of collision activation of the [M+H](+) spectrum were therefore examined. Positive ion MS3 spectra obtained in the ion trap from the gamma -glutamate cleavage products of FOG(7) and its derivative (d(7)-FOG(7)) afforded an abundant ion not observed in spectra generated from the cysteinyl leukotrienes. Formation of this fragment ion likely occurred via a McLafferty-type rearrangement to afford cleavage of the C6 -C7 bond adjacent to the sulfur atom and was valuable for the identification of the structure of FOG(7) and defining the biosynthetic pathway as a 1,4-Michael addition of glutathione to 5-oxo-eicosatetraenoic acid (5-oxo-ETE). (C) 2001 American Society for Mass Spectrometry.