Resolution of 4-(4-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4yl)-1(2H)-phthalazinone enantiomers in plasma with frit-FAB LC-MS using a conalbumin column

A new column-switching method for analysis of drug enantiomers in plasma has been developed with liquid chromatography-frit fast atom bombardment mass spectrometry in combination with a chiral resolution column, which consists of conalbumin (egg-white glycoprotein) immobilized on silica gel and can be used in the reversed-phase separation mode. This method makes it possible to inject a large volume of deproteinized plasma and obtain resolution of drug enantiomers with high sensitivity. The optimum mobile phase, including a non-volatile buffer such as phosphate buffer, for separation of drugs from a large amount of endogenous compounds can be used, because of inclusion of a trapping column with a desalting function. This method is very simple and rapid, and should be very powerful in studies requiring high-sensitivity analysis with chiral separation of drugs from biological samples such as plasma.