Thermal and photolytic decomposition of methotrexate in aqueous solutions

J Pharm Sci. 1978 Apr;67(4):526-31. doi: 10.1002/jps.2600670422.


The chemical kinetics of thermal and photolytic degradation of methotrexate in aqueous solutions were studied. At above pH 7 and 85 degrees, methotrexate hydrolyzed to yield mainly N10-Methylpteroylglutamic acid. The hydrolysis rate followed first-order kinetics with respect to methotrexate concentration and increases 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 marked when stored in the original vial at room temperature.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Hot Temperature
  • Injections
  • Methotrexate* / analysis
  • Methotrexate* / radiation effects
  • Photolysis
  • Solutions


  • Solutions
  • Methotrexate