Stability of trimetrexate, a new non-classical antifolate, in infusion solutions

A prerequisite for the prolonged infusion of a drug via a totally implanted drug delivery system is that the drug solution must be sufficiently stable at physiological temperatures to endure the time intervals between drug replacement or pump refills. Consequently, the stability of the chemotherapeutic agents can influence the dosing accuracy and ultimately the achievement of the desired therapeutic goal. The chemical stability of the pharmaceutical preparation Trimetrexate (TMQ) glucuronate, a non-classical, lipophilic antifolate, has been characterized. Incubation of TMQ (prepared in sterile water to a concentration of 5.0 mg/ml) in sterile, amber glass vials at 37 degrees C for 56 days resulted in a degradation rate constant of 0.0134 +/- 0.002 day-1 and a half-life of 51.6 +/- 0.8 days. The major degradation product has been identified as (2,4-diamino-5-methyl-6-carboxaldehyde)quinazoline. Ten percent TMQ degradation would occur by 7.9 days of incubation under these conditions.