A Systematic Analytical Quality By Design Approach For Estimation Of Decitabine And Cedazuridine Combined Pharmaceutical Formulations Using RP-HPLC

Authors

  • A. Ramyasree , S. Umadevi

DOI:

https://doi.org/10.47750/pnr.2022.13.S10.569

Abstract

The present research work emphasises systematic development of a simple, fast, sensitive, reproducible and cost-effective reversed-phase high-performance liquid chromatographic (RP-HPLC) method, applying the principles of Quality-by-Design (QbD) for analysis of Decitabine (DCT) and Cedazuridine (CDZ) in combined oral pharmaceutical formulation. Preliminary risk assessment was performed and then screening studies were carried out using a four-factor-two-run fractional factorial design (FFD). Eventually, optimization studies were executed out employing a central composite design (CCD) with flow rate and mobile phase ratio as the critical method parameters (CMPs), and tailing factor (TF), % assay and theoretical plate count (TPC) as the critical analytical attributes (CAAs). The optimized RP-HPLC method for determination of DCT and CDZ used X-Terra C18 column (250 X 4.6mm, 5μm particle size) and mobile phase consist of 0.1%OPA: Methanol, 45:55 v/v. The retention time for DCT and CDZ was found to be 2.923min and 3.948min. The method was linear in the range of 10–200 μg/ml with 0.992 correlation coefficient. The % RSD for repeatability, intraday, and inter day precision was found to be less than 2% indicating the optimized method was precise. The LOD and LOQ were 0.22μg/ml, 0.24μg/ml and 0.67 μg/ml,0.72μg/ml, respectively. According to the ICH guidelines, the percent recovery of spiked samples ranged between 99.57 1.47 and 100.79 1.73. The developed method was validated in accordance with the ICH Q2 (R1) guidelines, as well as the principles and science of analytical quality by design (AQbD), for estimating DCT and CDZ in bulk drugs and marketed formulations with a high degree of linearity, accuracy, precision, sensitivity, and robustness.

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Published

2022-12-31 — Updated on 2022-12-31

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How to Cite

A Systematic Analytical Quality By Design Approach For Estimation Of Decitabine And Cedazuridine Combined Pharmaceutical Formulations Using RP-HPLC. (2022). Journal of Pharmaceutical Negative Results, 4697-4705. https://doi.org/10.47750/pnr.2022.13.S10.569