Kinetics of degradation of methotrexate in aqueous solution

The chemical stability of methotrexate (I) in aqueous solution protected from light was studied utilizing an HPLC procedure. The investigation of the kinetics of degradation took place in aqueous buffer solutions at 85°C over the pH-range of 0–12. The pH-rate profile obtained from first-order kinetic plots showed maximum stability at about pH 7. An Arrhenius-type plot indicated a shelf-life at pK ~ 8.5 of about 4.5 years at 25 °C.At pH above 6.5 N¹⁰-methyl-folic acid (II) was the only degradation product while in acidic solution several compounds are formed.