BACKGROUND: In bioanalysis, phospholipids may affect the precision and accuracy 
of LC-MS/MS methods and compromise the quality of the results, especially when 
samples in complex biomatrices are extracted by protein precipitation 
techniques.
RESULTS: It was found that the retentive behavior of both common pharmaceuticals 
and physiologically relevant phospholipids under bare silica 
hydrophilic-interaction LC (HILIC) is more predictable than under reversed-phase 
conditions. In particular, the retention time of phospholipids was not 
significantly affected by varying the salt and acid modifiers in the mobile 
phases, but common pharmaceuticals can be shifted away from these phospholipid 
interferences through mobile phase modifiers. Several mass spectrometric 
techniques were applied to confirm this finding.
CONCLUSION: HILIC chromatography is a valued tool in the development of robust 
bioanalytical assays with minimal and predictable phospholipid interferences. 
Furthermore, addition of a small amount of ion-pairing additives can reliably 
move pharmaceutical compounds away from these suppressive regions.