Isolation and identification of a degradation product in a capsule formulation containing the elastase inhibitor, DMP 777

An unexpected degradation product, greater than 0.10%,was observed in a DMP 777 capsule formulation stored at 40 degreesC/75% r.h. for 3 months and 25 degreesC/60%: r.h. for 2 years. The degradant of interest was prepared in quantity by refluxing the drug substance in dilute acid. A preparative HPLC method was developed to separate the various degradants and to collect eac h as a separate Fraction. Each Fraction was analyzed by the analytical HPLC gradient test method to assure positive identification of each peak and to correlate each peak to the original capsule sample. Key isolated degradati on products were used for structure elucidation with mass spectrometry. and NMR. The major degradant of interest in the capsule formulation was found to be a carboxylic acid resulting from the acid hydrolysis of an amide bond . (C) 2001 Published by Elsevier Science B.V. All rights reserved.