QbD green analytical procedure for Novel study of a genotoxic and carcinogenic compound trace determination in physiological solution compatibility

Abstract

Regulatory bodies more focusses on the safety and efficacy of the pharmaceuticals, through this work we want to express the necessary control of 5-Hydroxymethyl furfural (5-HMF) impurity level in intra-venous (IV) injections. Genotoxic and carcinogenic compound 5-HMF determination in IV injections was determined by using the simple, sensitive, green, and eco-friendly HPLC method. Box-Behnken Design (BBD) was utilized to optimize the final method conditions prior to method validation, resulting in 15 design of experiments (DOE) using critical method parameters (CMPS) and critical assumptions. The identification and quantification were done with Phenomenex prodigy C8 (150 × 4.6) mm, 5 μm column with a flow rate of 0.6 mL/min. The peak detection was done at 284 nm and with a total run time of 6 min. The mobile phase consists of 0.1 M potassium dihydrogen phosphate (PDP) pH 2.5 buffer and acetonitrile (ACN) in the ratio of 80:20 (v/v) used for the isocratic elution. The method was validated as per the current regulatory guidelines. The accuracy results from LOQ to 150% level were attained between 95.1% and 103.4%. The 5-HMF response is linear from LOQ to 150% with a correlation coefficient (r) > 0.999. The %coefficient of variation (CV) from method precision and intermediate precision (n = 6) results were found to be 1.67% and 3.45%, respectively. Trace analysis of 5-HMF was done in selected IV injections Pancuronium Bromide (PMB), Meropenem (MPM), Doripenem (DPM), and Cefotaxime (CTM) injections at different time points. The method greenness was evaluated by utilizing the Green analytical procedure index (GAPI), Analytical GREEness (AGREE), National environmental procedure index (NEMI), and analytical eco-scale and concluded that the method is green.