Quality by design based analytical (RP-HPLC) method development and validation of coenzyme q10 in single and combination with clomiphene citrate: An extensive review

Analytical Quality by Design (AQbD) has emerged as a rigorous, science-driven framework that supports the development of robust and regulatory-compliant analytical procedures. Its application to RP-HPLC has gained increasing prominence in pharmaceutical and biopharmaceutical research due to its ability to enhance method precision, reliability, and overall process understanding. This review examines the principles, workflow, and practical implementation of AQbD within RP-HPLC method development, with particular emphasis on the simultaneous analysis of Coenzyme Q10 (CoQ10) and Clomiphene Citrate (CC). Key elements such as defining the analytical target profile, identifying critical method attributes, conducting structured risk assessment, applying multivariate design of experiments, establishing the method operable design region, and integrating lifecycle-based control strategies are critically evaluated. Evidence from contemporary literature demonstrates that AQbD-guided methods outperform traditional trial-and-error approaches by reducing variability, strengthening method robustness, and providing a defensible scientific rationale for regulatory submissions. Given the increasing clinical and analytical interest in CoQ10 and CC, especially when evaluated or formulated together, AQbD offers an effective pathway for developing reliable, adaptable, and high-quality chromatographic methods. Overall, AQbD represents a forward-looking approach that supports product quality, patient safety, and sustained innovation in pharmaceutical analytical science.