Abstract The concept of analytical quality by design (AQbD) has recently gained prominence and offers multiple advantages for the pharmaceutical industry. AQbD is an approach that uses risk management to develop robust analytical methods that comply with regulatory requirements. Menthol is a standard raw material used in formulating various pharmaceutical products, including creams, ointments, and salves. We implemented an analytical quality by design (AQbD) approach to establish optimal parameters for the identification and quantification of menthol. This methodology utilizes gas chromatography coupled with an internal standard to create a reliable, reproducible, and cost-effective analytical method. In developing the method through AQbD, we first defined the analytical target profile (ATP). We employed risk management tools to identify critical analytical attributes (CAAs), such as resolution, retention time, theoretical plates, capacity factors, and choking factors. We also determined critical process parameters (CPPs), including oven temperature and flow rate. The influence of CPPs on CAAs was assessed using a factorial experimental design. Subsequently, we established the method operable region (MODR) to pinpoint the optimal conditions and specified parameters for each CAA, as indicated by response surface diagrams. The optimized method was validated in accordance with international regulatory guidelines to ensure system suitability. This validation process included evaluations of linearity, accuracy, and precision, as well as the determination of limits of detection and quantification. The results confirmed that the conditions were appropriate for analyzing menthol using gas chromatography with an internal standard.
Puentes et al. (Sat,) studied this question.