Spirohydantoin mustard (I) is a rationally designed anti-tumor agent with substantial in vivo activity against intracranially implanted tumors in mice. However, hydrolysis of I was much faster than that of mechlorethamine hydrochloride or melphalan, two parenterally administered mustards. The hydrolysis products of I were identified by GC-MS of their silylated derivatives. The decomposition of I (at 25 degrees in 10% dimethylacetamide at pH 4-6), as monitored by GLC was pseudo first-order. The half-life of I ranged from 20 min at pH 4.0 to 14 min at pH 6.0. Nonionic surfactants enhanced the stability of I, but this effect was diminished at lower pH, presumably due to decreased solubility of I in the micelle as more drug was protonated. Several dilute parenterally suitable solvents exhibited no marked effect on the hydrolysis of I. The drug was most stable in a 10% fat emulsion system where the time for 10% decomposition of I was 49 +/- 5 min. Plots of the concentration of I versus time were linear indicating the disappearance was zero order in the 10% fat emulsion system.