Minimization of ion suppression in LC-MS/MS analysis through the application of strong cation exchange solid-phase extraction (SCX-SPE).

Ion suppression of drug response is a major source of imprecision for bioanalytical analysis using LC-MS/MS. Endogenous phospholipids cause ion suppression in both positive ESI and negative ESI modes and must be removed or resolved chromatographically. Three types of ion-exchange solid-phase extraction mediums were evaluated to determine their abilities to remove phospholipids. It was determined that although mixed mode phases fulfills the requirements of retaining both analytes and diverse metabolites, reverse phase retention mechanisms are detrimental in eliminating ion suppression caused by late eluting phospholipids. If an analyte and its metabolites can be retained using an ion-exchange mechanism alone, mixed mode extraction phases should be avoided.