Development, Optimization, andValidation of a Quality by Design-assistedReverse-phase High-performance LiquidChromatography Method for ImpurityProfiling of Imeglimin Hydrochloride“Quality by Design Assisted ImpurityProfiling of Imeglimin Hydrochloride”
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Abstract
Introduction: The newly-approved tetrahydrotriazine-based antidiabetic drug imeglimin hydrochloride (IMGH)
might be contained process- and degradation-related impurities, which require sensitive and robust analytical
control in compliance with regulatory requirements. In this paper, a Quality by Design (QbD)-supported Reversed-
Phase High-Performance Liquid Chromatography (RP-HPLC) technique of comprehensive impurity profiling of
IMGH in pharmaceutical dosage forms is designed, optimized, and validated. Materials and Methods: A QbD-
enabled systematic method based on the central composite design was employed to establish the influence of key
technique parameters, such as mobile phase composition and pH, on chromatographic responses, such as retention
duration, theoretical plates and percent recovery. To obtain optimum separation, a Phenomenex ODS C18 column
(250 × 4.6 mm, 5.0 mm) was used with 10 mM acetate buffer: ACN (30:70) as the mobile phase and 1.0 ml/min
flow rate, column temperature of 30°C, and ultraviolet detection at 240 nm. Discussion and Conclusion: The
optimized method was validated in accordance with ICH Q2(R1) and Q3B guidelines, demonstrating excellent
linearity (R2 = 0.999), precision, accuracy, specificity, robustness, and sensitivity. IMGH and its associated
impurity, N2, N2,6-trimethyl-1,3,5-triazine-2,4-diamine were found to have limits of detection of 2.158 μg/mL
and 0.04117 μg/mL, respectively, and limits of quantification of 6.021 μg/ml and 0.125 μg/ml, respectively.
Recovery studies confirmed the accuracy of the method, with recoveries within acceptable regulatory limits.
In order to ensure product safety and consistency, the suggested QbD-based RP-HPLC approach provides a
straightforward, reliable, and legally compliant analytical instrument for routine quality control and impurity
monitoring of IMGH in pharmaceutical formulations.
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