Chlorambucil: stability of solutions during preparation and storage

A stability-indicating high-performance liquid chromatographic method has been used to investigate the stability of chlorambucil in solution. Dissolved in ethanol and diluted with 150 mM NaCl (NS), the drug was found to be very much more stable frozen, with a value for 5% degraded (t0.95) of approximately 8 months at -70 degrees C. The presence of agar or cells, and freezing and thawing the solution did not reduce the concentration of chlorambucil significantly. The drug seemed to adsorb to polyvinyl chloride (PVC) infusion bags (but to no other container material) and also to all three filtration units tested. Intense light increased the degradation of the drug, whilst the addition of 10% serum to chlorambucil in medium increased the drug's stability four fold. Dilution with NS of stock solutions of chlorambucil in ethanol resulted in supersaturated solutions of the drug. For preparation of the drug for in vitro drug sensitivity assays, the results suggest that care should be taken in the initial dilution of the drug; not to use filtration units to sterilize solutions; to anticipate different degradation rates (and therefore cytotoxicity) if the serum concentration in medium is altered; and to avoid the use of PVC.