Identification of porphyrin modified photosensitizer porfimer sodium and its precursors by high performance liquid chromatography and mass spectrometry

Abstract

Photodit ® (porfimer sodium) is a complex mixture of porphyrin-modified oligomers that has demonstrated high photoactivity during photodynamic therapy of malignant tumors. Hematoporphyrin derivative monomer precursors of Photodit ® and its oligomers were analyzed using liquid chromatography and mass spectrometry to determine their chemical composition and structures. Hematoporphyrin ( M-3), O, O′-diacetylhematoporphyrin ( M-6), and isomers of 8(-3)-hydroxyethyl-3(-8)-vinyldeuteroporphyrin ( M-2), 8(-3)-(1-acetoxyethyl)-3(-8)-vinyldeuteroporphyrin ( M-4), and O-acetylhematoporphyrin ( M-5), in ratio 0.59:0.94:0.21:0.34:1.00, were identified as hematoporphyrin derivative monomer precursors. The main compounds of Photodit ® as a porfimer sodium salt were dimers: D-1 {di-[8(-3)-hydroxyethyl-3(-8)-vinyldeuteroporphyrin] ether}, D-2 {[Hematoporphyrin-8(-3)-hydroxyethyl-3(-8)-vinyldeutroporphyrin] ether}, and D-3 {Dihematoporphyrin ether} in ratio 0.51:1.00:0.50, and trimers: T-1 {(M-2)–(D-2) ether}, T-2 {(D-2)–(M-3) ether}, and T-3 {(D-3)–(M-3) ether} in ratio 0.98:1.00:0.44, respectively. An average oligomer length of 2.23 porphyrin units was determined.