Characterization of Phosphatidylcholine Oxidation Products by MALDI MS<sup><i>n</i></sup>

Abstract

Phospholipid oxidation has been implicated in the pathogenesis and progression of numerous age-related and neurodegenerative diseases. Despite these implications, this broad class of biomolecules remains poorly characterized. In this work, the fragmentation patterns of [M + H]<sup>+</sup> and [M + Na]<sup>+</sup> ions of intact phosphatidylcholine oxidation products (OxPCs) were characterized by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI MS<sup><i>n</i></sup>, <i>n</i> = 2, 3, and 4). MS<sup>2</sup> of both the [M + H]<sup>+</sup> and [M + Na]<sup>+</sup> ions of short-chain OxPCs yielded product ions related to the PC headgroup and the fatty acid substituents. MS<sup>3</sup> of the [M + Na – N­(CH<sub>3</sub>)<sub>3</sub>]<sup>+</sup> ions yielded fragmentation indicative of the OxPC modification; specifically, a product ion corresponding to the neutral loss of CO<sub>2</sub> (NL of 44) was observed for OxPCs containing a terminal carboxylic acid rather than an aldehyde. Furthermore, MS<sup>4</sup> of the [M + Na – HPO<sub>4</sub>(CH<sub>2</sub>)<sub>2</sub>N­(CH<sub>3</sub>)<sub>3</sub>]<sup>+</sup> ions resulted in fragmentation pathways dependent on the <i>sn</i>-2 fatty acid chain length and type of functional group(s). Specifically, CHO-containing OxPCs with palmitic acid esterified to the <i>sn</i>-1 position of the glycerol backbone yielded a NL of 254, 2 u less than the nominal mass of palmitic acid, whereas the analogous terminal COOH-containing OxPCs demonstrated a NL of 256. Finally, the presence of a γ-ketone relative to the terminal carboxyl group resulted in C–C bond cleavages along the <i>sn</i>-2 substituent, providing diagnostic product ions for keto-containing OxPCs. This work illustrates the enhanced selectivity afforded by MS<sup><i>n</i></sup> on the linear ion trap and develops a method for the identification of individual products of PC oxidation

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