Electrospray ionization and tandem mass spectrometry of cysteinyl eicosanoids: leukotriene C 4 and FOG 7

Abstract

The cysteinyl leukotrienes, LTC 4, LTD 4 and LTE 4, and the recently described cysteinyl eicosanoid, 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG 7) 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 MS 3 spectra obtained in the ion trap from the γ-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).