THERMAL AND PHOTOLYTIC DECOMPOSITION OF METHOTREXATE IN AQUEOUS-SOLUTIONS

The chemical kinetics of thermal and photolytic degradation of methotrexate in aqueous solutions were studied. At above pH 7 and 85°, methotrexate hydrolyzed to yield mainly N10‐methylpteroylglutamic acid. The hydrolysis rate followed first‐order kinetics with respect to methotrexate concentration and increased rapidly above pH 9. When methotrexate solutions were kept under laboratory fluorescent light, the major degradation products were 2,4‐diamino‐6‐pteridinecarbaldehyde, 2,4‐diamino‐6‐pteridinecarboxylic acid, and p‐aminobenzoylglutamic acid. The photolytic reaction followed zero‐order kinetics with respect to methotrexate concentration and was catalyzed by bicarbonate ion. Evidence is presented for a proposed sequential cleavage of methotrexate by a free radical mechanism for the photolysis. Commercial parenteral methotrexate was found to be quite stable as marketed when stored in the original vial at room temperature. Copyright © 1978 Wiley‐Liss, Inc., A Wiley Company