Abstract
In-process control (IPC) is an important task during chemical syntheses in pharmaceutical industry. Despite the fact that each chemical reaction is unique, the most common analytical technique used for IPC analysis is high performance liquid chromatography (HPLC). Today, the so-called “Quality by Design” (QbD) principle is often being applied rather than “Trial and Error” approach for HPLC method development. The QbD approach requires only for a very few experimental measurements to find the appropriate stationary phase and optimal chromatographic conditions such as the composition of mobile phase, gradient steepness or time (), temperature (T), and mobile phase pH. In this study, the applicability of a multifactorial liquid chromatographic optimization software was studied in an extended knowledge space. Using state-of-the-art ultra-high performance liquid chromatography (UHPLC), the analysis time can significantly be shortened. By using UHPLC, it is possible to analyse the composition of the reaction mixture within few minutes. In this work, a mixture of route of synthesis of apixaban was analysed on short narrow bore column (50 × 2.1 mm, packed with sub-2 µm particles) resulting in short analysis time. The aim of the study was to cover a relatively narrow range of method parameters (, T, pH) in order to find a robust working point (zone). The results of the virtual (modeled) robustness testing were systematically compared to experimental measurements and Design of Experiments (DoE) based predictions.
Highlights
The demands for enhancing the speed of method development are continuously growing nowadays
Apixaban and its intermediates were used as test solutes, which were formed during the manufacturing process [9]
The flow chart of the synthesis is presented on Figure 1
Summary
The demands for enhancing the speed of method development are continuously growing nowadays. One needs to work out separation methods that are reliable and robust as well as time and solvent efficient. The conception of QbD is spreading through pharmaceutical production and through the establishment of analytical methods [2]. In the synthesis of active pharmaceutical ingredients (API), analytical support is very important. The separation of API and its impurities is a necessary step in the control of pharmaceutical products. The chemical structure of the impurities is quite different compared to the API. In most cases, reversed-phase liquid chromatography (RPLC) is the method of choice to analyze those API samples. In RPLC conditions, several parameters influence the quality of the separation. The other important parameters are the composition of the mobile phase (%B or time of gradient, tG), pH, and temperature among others [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
