HPLC METHOD DEVELOPMENT FOR AG-85 AND BENZYL ALCOHOL IN ANHYDROUS TOPICAL FORMULATIONS

AG-85, a lipophilic drug synthesized by rational drug design, is inhib itory to cellular growth in vitro by inhibition of the enzyme thymidyl ate synthase which catalyses the rate-limiting step in the de novo syn thesis of thymidine nucleotides (Appelt et al:, J. Med. Chem., 34 (199 1) 1925-1934). A pharmaceutically elegant anhydrous topical formulatio n of AG-85 was developed for treatment of psoriasis (Pavliv et al., In t. J. Pharm., (1994) in press). Benzyl alcohol was used as a preservat ive in the topical formulation. HPLC methods were developed and valida ted to quantstate AG-85, AG-85 impurities, and benzyl alcohol. Precisi on, accuracy, limit of quantitation (for Category II quantitative), se lectivity, linearity range,and ruggedness were the analytical paramete rs addressed for these methods. The validated methods meet current GMP requirements.