ASSAY OF THE ENANTIOMERS OF IBUTILIDE AND ARTILIDE USING SOLID-PHASE EXTRACTION, DERIVATIZATION, AND ACHIRAL CHIRAL COLUMN-SWITCHING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Ibutilide fumarate and artilide fumarate, new drugs for the treatment of cardiac arrhythmias, each contain a stereogenic center bearing a se condary alcohol group. Reversed-phase achiral-chiral column-switching HPLC separations of the enantiomers of each compound were developed an d validated for quantitation in plasma and other biofluids. The key co mponent of the method was derivatization with 1-naphthyl isocyanate, w hich enhanced the sensitivity of fluorescence detection and enabled th e enantiomers to be separated on a Pirkle column (covalent 3,5-denitro benzoyl-D-phenylglycine stationary phase). The lower limit of quantita tion of ibutilide fumarate was typically 0.1 ng/ml or less of each ena ntiomer in 1 ml of plasma. Two of the special features of the column-s witching system included operation with two samples in the system at o ne time, which reduced analysis time to 16 min/sample for ibutilide an d 19 min/sample for artilide, and a relay-operated switching of detect or outputs, which allowed achiral and chiral column chromatographic da ta to be gathered from two detectors into a single data acquisition ch annel.