New safe medicines faster: the role of analytical chemistry

Abstract

One of the bottlenecks to be tackled in the course of reaching the goal summarised by the slogan “New Safe Medicines Faster” is estimation of impurity profiles. The importance of impurity profiling in different phases of drug R&D is described. A general scheme is proposed for the strategy and the rational use of chromatographic, spectroscopic and hyphenated techniques in impurity profiling. Two practical examples are given: structure elucidation of an impurity [3α,17β-diacetoxy-2β-(4′,4′-dimethylpiperazinium-1′-yl)-16β-(1′,2′,3′,4′-tetrahydro-4′,4′-dimethylpyrazinium-1'-yl)-5α-androstane dibromide] in pipecuronium bromide [3α,17β-diacetoxy-2β,16β-bis(4′,4′-dimethylpiperazinium-1′-yl)-5α-androstane dibromide]; and, estimation of the mechanism of the acid- and base-catalysed, as well as oxidative, degradation of mazipredone [11β,17α-dihydroxy-21-(4′-methylpiperazin-1′-yl)-pregna-1,4-dien-3,20-dione hydrochloride].