Physicochemical factors governing the partition of pramipexole and its five impurities in microemulsion liquid chromatographic systems

Abstract

As microemulsões, quando usadas como fase móvel, representam uma ferramenta cromatográfica poderosa devido à sua estrutura polifásica. O objetivo deste estudo foi investigar a influência da composição da fase móvel e as propriedades das gotículas resultantes da microemulsão, bem como a lipofilicidade da fase estacionária no comportamento cromatográfico de pramipexol e suas cinco impurezas. A investigação foi realizada de acordo com o plano experimental definido pelo planejamento fatorial completo 2 4 com quatro repetições do ponto central. Embora o mais afetado pelas características da coluna tenha sido o último eluente, a substância mais lipofílica, a composição e as características das gotículas de microemulsão foram igualmente importantes, de modo que o sistema de partição gotículas de microemulsão/fase estacionária provou ser o mais significativo. A lipofilicidade da fase estacionária não afetou o componente mais hidrofílico e somente o sistema de partição gotículas de microemulsão/volume do eluente causou impacto em seu comportamento. Para a separação do par crítico, foram notados efeitos quase iguais dos sistemas de partição gotículas de microemulsão/fase estacionária e volume do eluente/fase estacionária.Microemulsions when used as mobile phases represent a very powerful chromatographic tool due to their polyphase structure. The aim of this study was to investigate the influence of the mobile phase composition and resulting microemulsion droplet's properties, as well as the stationary phase lipophilicity on the chromatographic behavior of pramipexole and its five impurities. Investigation was carried out according to the experimental plan defined by a full factorial design 2 4 with four central point replications. While the most affected by column characteristics was the last eluting, most lipophilic substance, the composition and characteristics of microemulsion droplets were equally important, so the partition system microemulsion droplets/stationary phase proved to be the most significant. Stationary phase lipophilicity did not affect the most hydrophilic component and only the partition system microemulsion droplets/bulk of the eluent impacted its behavior. For the separation of the critical pair, almost equal effects of the microemulsion droplets/stationary phase and bulk of the eluent/stationary phase partition systems were noted.

Synthesis of Impurities of Pramipexole Dihydrochloride

“…Some of them originate from the manufacturing process of the active pharmaceutical ingredient (API). Others may be caused by oxidation or degradation of pramipexole in the process of preparation and storage . For instance, Nishimura et al reported that 5 might be caused by photodegradation of pramipexole in the preparation and explained possible mechanisms for this in the solid state and the liquid state.…”

Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles

“…So far pramipexole and its impurities have been analyzed in different liquid chromatographic systems [22][23][24][25][26], but this is the first time in literature that this approach is suggested.…”