RESUMEN
Automation of analytical sample preparation and testing is always attractive due to its high efficiency and continuous operation, but it can also be very challenging due to the operational complexity and method development. Studies focused on method development in automated systems are extremely rare and little has been published on the subject. In this paper, we investigate several unique and advanced aspects of this subject. The example product is selected containing two APIs to be tested by a single method to be productive. The product strengths of the two APIs are significantly different, making development of a single method much more challenging. In addition, we use a "green chemistry" approach, avoiding any organic solvent in the dissolving media in order to achieve an environmentally friendly solution. The selection and optimization of several key operational parameters are then discussed. The successful method is achieved using a new strategy called "Automated Online Standard (AO-STD)" methodology. This novel approach is compared to the manual operation procedure. The proposed approach can substantially reduce the method transfer time, generally considered the biggest obstacle to practical deployment of automated systems. The automated system applied in this paper is most suitable for content uniformity testing, but is also applicable for potency assays, blend uniformity testing, and degradation product tests.
Asunto(s)
Bioensayo , AutomatizaciónRESUMEN
Relative Response Factors (RRFs) can be used for quantitation of one compound against another and it is widely used for Impurity analysis of pharmaceutical products; however, the application in potency assay is limited. Through an extensive study shown in this paper, it can be concluded that using the "RRF methodology" for potency assay is much more challenging compared to impurity analysis, due to the much tighter criteria required for potency analysis. The effects of instrument settings, which are rarely discussed or recognized in current HPLC analytical method development and quality release testing, are discussed. These factors impact the RRF just as much as other commonly recognized HPLC parameters. The effects of UV detector settings, i.e. Slit Width, Step Width, Band Width, and Data Collection Module, have been explored. This phenomenon has been demonstrated using three compounds to observe the impact of their quantitation due to the significant RRF variations. Finally, principles to reduce RRF variations have been discussed, and practical considerations of RRF application to method development and method transfer are provided.