QUANTITATIVE PROFILING OF PHOSPHATIDYLETHANOL MOLECULAR SPECIES IN BLOOD OF HEAVY AND SOCIAL DRINKERS

Heavy alcohol consumption places a substantial burden on health all over the world. Metabolites of alcohol evoke alterations that lead to tissue damage in many organs. Phosphatidylethanol (PEth) is a unique phospholipid formed in the cellular membranes during the metabolism of ethanol after alcohol consumption. PEth has attracted special attention as it is postulated to be a reliable marker of long-term heavy alcohol consumption. Recent experiments have demonstrated the presence of different homologues of PEth in blood, revealing that it is not a single molecular species but a group of phospholipids with a common nonpolar phosphoethanol head group onto which 2 fatty acid moieties are attached at positions sn-1 and sn-2. The aim of the present study was to investigate the distribution of PEth molecular species in blood collected from heavy and social drinkers by means of two different analytical techniques: capillary electrophoresis and high-performance liquid chromatography, both coupled to a mass spectrometric detector. The above-mentioned methods were developed and validated according to international forensic toxicology guidelines, and applied to the analysis of real blood samples collected in a clinical setting. The quantitative profiling of PEth homologues in heavy drinkers showed that PEth 16:0/18:1 and 16:0/18:2 are the predominant species accounting on average for 46% and 28%, respectively, of total PEth. Due to inter-individual variations, PEth 16:0/18:2 was sometimes the major molecular species, whereas PEth 18:1/18:1 and 18:0/18:2 made up 11% of total PEth, and PEth 18:1/18:2 and 16:0/20:3 about 6%. Due to the high sensitivity of the liquid-chromatography high-resolution mass spectrometry method, it was possible to detect the two most abundant PEth homologues (PEth 16:0/18:1 and 16:0/18:2) also in blood of social drinkers. These results underline the importance of further research in order to characterize the formation and degradation rates of singular PEth molecular species, determine the most appropriate cut-off for each species, highlight the possible clinical advantages of focusing on distinct homologues instead of on total PEth, and to determine whether this marker of chronic alcohol abuse could also be utilized for detecting single episodes of heavy drinking (“binge drinking”).