THE COMPOSITION OF PHOTOFRIN-II

The compositions of Photofrin II and haematoporphyrin derivative (HPD) were examined. Dihaematoporphyrin ester was unambiguously synthesized and shown by high performance liquid chromatography (HPLC) not to be a significant component of Photofrin II. Hydrolysis studies showed the presence of an acid-stable oligomer in Photofrin II which comprised about 40% of the total sample. A dimer derivative was isolated from this oligomeric material by fully dehydrating the methyl-esterified acidic hydrolysis product of Photofrin II. The structure of this dimer, in which two porphyrin units are linked by a three-carbon bridge containing a double bond and a methyl group, was determined by nuclear magnetic resonance (NMR) and fast atom bombardment (FAB) mass spectrometry. An analogous trimer was also isolated and identified. Structures for the hydroxyl-containing precursors to the dimer and trimer, and for the acid-stable oligomeric material in Photofrin II, are suggested. The acid-stable oligomeric material is produced in the sodium hydroxide polymerization step of the preparation of Photofrin II. © 1990.