PHARMACEUTICAL ANALYSIS OF 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE

8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) has recently entered clinical trials as a new anticancer drug. 8-Cl-cAMP can undergo metabolism/degradation to nucleotides (8-Cl-AMP; 8-Cl-IMP), nucleosides (8-Cl-adenosine; 8-Cl-inosine) and bases (8-Cl-adenine; 8-Cl-xanthine and 8-Cl-hypoxanthine). A reversed-phase, gradient elution high-performance liquid chromatographic method is described which can resolve all the above from their nonchlorinated naturally occurring counterparts and 8-Bromo-cAMP. The assay was then utilized to perform pharmaceutical evaluations on the 8-Cl-cAMP formulation. Sterilization by filtration (0.22 mu m pore size) resulted in no loss of material. Stability studies carried out in the cartridges used to continuously infuse (for 7 days) the drug to patients showed no significant degradation over 17 days. Purity determinations revealed the presence of up to nine impurities (related to adenine) and yielded a purity figure of 95.9-99.3% with considerable batch to batch variation.