Stability of 2,5-diaziridinyl-3,6-bis(2-hydroxyethylamino)-1,4-benzoquinone (BZQ; NSC 224070) in aqueous solutions by high-performance liquid chromatography.

Abstract

The stability of the potential antitumour agent 2,5-diaziridinyl-3,6-bis(2 -hydroxyethylamino)-1,4-benzoquinone (BZQ; NSC 224070) has been investigated by high-performance liquid chromatography. At 22 degrees C in 0.05M buffer, BZQ was most stable at pH 9 with an apparent first-order rate constant (k) of about 0.014 h-1. There was reduced stability at pH values above and below 9.0. At a pH of 3 and 12 the values of k were 38 and 0.3 h-1, respectively. Stability of BZQ was adversely affected by increased temperatures (above 0 degrees C), increased buffer concentration and light. Solutions of BZQ could not be frozen for any length of time, as the drug precipitated out in a form that would not redissolve (possibly a polymer). For parenteral administration to patients, it is suggested that BZQ would be most stable in 1.26% sodium bicarbonate solution when at room temperature, under normal laboratory lighting, 5% of the drug degraded (t0.95) in 5.5 h. Increased stability is obtainable in this medium by refrigeration and vigorous exclusion of light. Long term (24 h) infusions of BZQ could be considered in hypotonic sodium bicarbonate (30 mM) with careful exclusion of light as long as the volume of the infusion was small, e.g. 1 ml/h. Under these conditions t0.95 was 42 h at 21.5 degrees C.