LC/MS provides an effective resolution and identification of intact molecular species of natural glycerophospholipids, especially when combined with reversed phase HPLC and MS/MS. The oxo-glycerophospholipids (hydroxides, epoxides, isoprostanes and others) when present, yield mixtures of lipids, where difficulties arise due to chemical instability and presence of isobaric components with similar chromatographic and mass spectrometric properties. The above problems are further complicated, when isobaric ether glycerophospholipids are present. We had previously observed that group V sPLA2 preferentially hydrolyses the oligoenoic species of GroPChos, while group X sPLA2 favors the hydrolysis of the polyunsaturated GroPCho species, both failing to hydrolyze the plasmanyl and plasmenyl cholines, which accumulate in the hydrolysis residue. Using human HDL3 as example, we now demonstrate that both group V and group X sPLA2s may be used to completely destroy the diacyl GroPChos and their oxo derivatives. The plasmanyl and plasmenyl cholines and their oxo-derivatives left in the digestion residue can then be resolved and quantified by normal phase LC/MS without interference from overlapping isobaric diacyl GroPChos and their oxo derivatives. The new method allows to search the ether glycerophospholipids for presence of epoxy, hydroxy, hydroperoxy and isoprostane derivatives, which have not been previously determined.