Characterization of decomposition products of maytansine

Analysis of outdated clinical samples of maytansine formulated in mannitol indicated that approximately 40% of the original maytansine content had decomposed. Chromatographic examination of these samples showed the presence of one major and multiple minor decomposition products. The major decomposition product was found to be maysine, a naturally occurring maytansinoid resulting from hydrolytic elimination of the C-3 ester side chain. Four minor decomposition products were isolated with the use of HPLC. All of these decomposition products were found to possess the C-3 ester side chain. However, other structural modifications were noted, especially in the region of the C-9 carbinolamide. Two of the minor decomposition products were tentatively identified as 10-epimaytansine and 9-epimaytansine. One minor decomposition product was found to contain a hydroxyl group at the benzylic C-15 position.