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 secondary alcohol group. Reversed-phase achiral-chiral column-switching HPLC separations of the enantiomers of each compound were developed and validated for quantitation in plasma and other biofluids. The key component of the method was derivatization with 1-naphthyl isocyanate, which enhanced the sensitivity of fluorescence detection and enabled the enantiomers to be separated on a Pirkle column (covalent 3,5-dinitrobenzoyl-D-phenylglycine stationary phase). The lower limit of quantitation of ibutilide fumarate was typically 0.1 ng/ml or less of each enantiomer in 1 ml of plasma. Two of the special features of the column-switching system included operation with two samples in the system at one time, which reduced analysis time to 16 min/sample for ibutilide and 19 min/sample for artilide, and a relay-operated switching of detector outputs, which allowed achiral and chiral column chromatographic data to be gathered from two detectors into a single data acquisition channel.
Hsu
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Upjohn Company, Kalamazoo, MI 49001, USA.
Walters
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RR
D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry
D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide; C095507:artilide