Reaction of lipids containing hydroxy groups with trimethylsulfonium hydroxide: formation of O-methyl derivatives

Base-catalyzed transesterification of acyl lipids with trimethylsulfonium hydroxide (TMSH) is an easy and convenient method for the preparation of fatty acid methyl esters (FAME) for gas chromatography (GC) analyses. We have found, however, that lipids containing hydroxy groups are partially converted to the corresponding O-methyl ether derivatives which may interfere with FAME in GC separations. For example, long-chain alcohols are found to be converted to alkyl methyl ethers, rac-1-O-alkylglycerols to the corresponding 2-O- and 3-O-monomethyl ethers, as well as 2,3-di-O-methyl ethers, hydroxy fatty acids to methoxy FAME, and cholesterol to cholesteryl 3 beta-methyl ether. From our results, it is obvious that TMSH derivatization method is not recommended without limitation for lipids containing hydroxy groups; it may be, however, of some diagnostic value for the analysis of such lipids by GC/mass spectrometry.