Probing the structure and stability of the tumor-localizing derivative of hematoporphyrin by reductive cleavage with LiAlH4.

Abstract

A procedure involving the use of the reducing agent lithium aluminum hydride (LiAlH4) has been designed to explore the nature of the oligomer linkages in the tumor-localizing component of hematoporphyrin derivative (HPD). High-performance liquid chromatography and fast-atom bombardment mass spectrometry were used to determine the reduction products. The results are consistent with a structure wherein ester linkages join hematoporphyrin molecules. The presence of minor amounts of ether-linked porphyrins was confirmed, and their origin was determined through the application of the chemical reduction process to HPD. An increased proportion of ether-linked porphyrins was detected during storage of HPD at room temperature or above. The commercial product Photofrin II, presumably an HPD preparation enriched in the dimer/oligomer fraction, was found to contain approximately 50% ether linkages. This product therefore differs from the corresponding fraction of freshly prepared HPD.