Integrative greenness, blueness and whiteness determination of analytical RP-HPLC method for identifying Imipenem, Cilastatin and Relebactam in combined tablet form followed by forced degradation studies

Abstract

Most clinically preferred, US FDA and EU approved anti-infective drug, a multi-component formulation of Imipenem (IPM), Cilastatin (CS) and Relebactum (REL). The combination is used in medicating the most complicated, gram-negative bacterial infections. Henceforth, it requires the development of selective, precise, accurate, robust analytical method. Hence the present work comprises RP-HPLC method development for determination of IPM, CS and REL. The detection is achieved by using new and apt conditions i.e., Discovery C₁₈ (4.6 × 150 mm, 5 µm) column, 0.01 N Potassium Dihydrogen Phosphate buffer: Acetonitrile (60:40) as mobile phase. The detection was found at short RT i.e., 2.32, 3.08, and 3.62-min for IPM, CS and REL correspondingly. Good sensitivity was observed, where LOD of 0.11 µg/ml (IPM), 0.14 µg/ml (CS), and 0.06 µg/ml (REL) was obtained. While, LOQ was noticed at 0.33 µg/ml (IPM), 0.43 µg/ml (CS) and 0.18 µg/ml (REL). As a counterpart, other study of forced degradation was also performed for the selected drugs at different extreme conditions. A sustainability evaluation has been done on the proposed method. The creative tools such as AGREE, GAPI, ChlorTox scale in green analytical counterpart were performed providing good score. Another BAGI software was opted as blue principle-evaluator, that resulted in a good score of 85 %. Highlighting the use of the most recent sustainability determination software, RGBfast model in present work with a good score of 74 %. Moreover, white and green evaluation has been performed in the form of comparative mode, for better understanding of the significance of current method.