CHROMATOGRAPHIC ANALYSIS OF RESIDUAL ACETATE IN BULK DRUGS

An ion chromatographic method for the determination of the residual ac etate in bulk drug was developed. The drug was MK0476 an LTD(4) antago nist. The compound also has a carboxyl functionality, which would inte rfere with the detection of the acetate ion. A solid phase extraction through a Sep-Pak cartridge was pursued for the removal of MK0476 from the matrix. Since the analyte does not have a chromophore, a mobile p hase containing trimesic acid facilitated its detection by indirect ph otometric detection. The separation was performed on a polymeric stron g anion exchange column. The influence of pH, concentration of trimesi c acid, and temperature were studied. Chloride ion was found to be a c ontaminant that was interfering in the analysis. To improve the separa tion between chloride and acetate ions, methanol was added to the mobi le phase, leading to complete separation between the two species. Reco very of the acetate ion was determined as 92.3%. The method was applie d to real samples with good results. It was shown to be sensitive for the determination of less than 0.001 mg/ml of acetate with a linear ra nge of 0.00036 to 0.074 mg/ml.