Method development on automated sample preparation system for content uniformity and assay testing in a product with multiple APIs and new strategy for quick development and application

Abstract

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.