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<p>The pharmaceutical industry is one of the fastest developing industries, and therefore, the chromatographic methods used to ensure the quality of products are constantly evolving, based on current regulatory requirements. Relevant guidelines state that a good understanding of the effects of all parameters on method performance should be predicted and controlled to ensure that test methods are safe and reliable. This quality by design-based approach is increasingly applied in chromatography. One of the pillars of this method development is the design space that results from pre-designed and systematically realized experiments, which contributes to a better understanding of the separation processes and provides flexibility and robustness to the final method. Modeling softwarewares can be used to experimental design and data evaluation, providing possibilities that empirical development does not allow, such as predicting optimal operating conditions or <italic>in silico</italic> robustness testing, to understand the separation process. This paper describes the steps of chromatographic method development according to the ICH Q14 guideline, keeping in mind the quality by design principles and taking advantage of the possibilities offered by the DryLab chromatographic modeling software. As an example, the development of an analytical method for the determination of the related substances of ezetimibe is presented, including the design of experiments, method optimization, robustness testing, validation, method specification and lifecycle management, and finally testing of the method applicability. We have demonstrated that experimental design-based retention modeling is an effective way of method development, and the <italic>in silico</italic> robustness testing is a reliable approach to identifying critical method parameters and setting up control strategies. In chromatographic method development, instead of using a rigid system based on strict and fixed rules, the understanding of separation processes offers higher flexibility. This paper aims to present and promote this new approach to those involved in chromatographic method development.</p>
</abstract>

The pharmaceutical industry is one of the fastest developing industries, and therefore, the chromatographic methods used to ensure the quality of products are constantly evolving, based on current regulatory requirements. Relevant guidelines state that a good understanding of the effects of all parameters on method performance should be predicted and controlled to ensure that test methods are safe and reliable. This quality by design-based approach is increasingly applied in chromatography. One of the pillars of this method development is the design space that results from pre-designed and systematically realized experiments, which contributes to a better understanding of the separation processes and provides flexibility and robustness to the final method. Modeling softwarewares can be used to experimental design and data evaluation, providing possibilities that empirical development does not allow, such as predicting optimal operating conditions or in silico robustness testing, to understand the separation process. This paper describes the steps of chromatographic method development according to the ICH Q14 guideline, keeping in mind the quality by design principles and taking advantage of the possibilities offered by the DryLab chromatographic modeling software. As an example, the development of an analytical method for the determination of the related substances of ezetimibe is presented, including the design of experiments, method optimization, robustness testing, validation, method specification and lifecycle management, and finally testing of the method applicability. We have demonstrated that experimental design-based retention modeling is an effective way of method development, and the in silico robustness testing is a reliable approach to identifying critical method parameters and setting up control strategies. In chromatographic method development, instead of using a rigid system based on strict and fixed rules, the understanding of separation processes offers higher flexibility. This paper aims to present and promote this new approach to those involved in chromatographic method development.

Quality by design-based method development for the determination of related substances of ezetimibe by high performance liquid chromatography

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures

Department of Pharmaceutical Industry and Management

Gedeon Richter Romania, Product Development Department

Gedeon Richter Romania, Analytical Development Department

Department of Pharmacology and Clinical Pharmacy

Semmelweis University, Faculty of Pharmacy

Bulletin of Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The pharmaceutical industry is one of the fastest developing industries, and therefore, the chromatographic methods used to ensure the quality of products are...

Quality by design-based method development for the determination of related substances of ezetimibe by high performance liquid chromatography

Published Online: Aug 31, 2023

Page range: 31 - 63

DOI: https://doi.org/10.2478/orvtudert-2022-0003

Keywords
quality by design, chromatography, DryLab, ezetimibe, ICH Q14

© 2023 Elek Ferencz et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Quality by design-based method development for the determination of related substances of ezetimibe by high performance liquid chromatography

Published Online: Aug 31, 2023

Page range: 31 - 63

DOI: https://doi.org/10.2478/orvtudert-2022-0003

Keywordsquality by design, chromatography, DryLab, ezetimibe, ICH Q14

© 2023 Elek Ferencz et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
quality by design, chromatography, DryLab, ezetimibe, ICH Q14