Eco-Friendly Synchronous Spectrofluorimetric Determination of Imipenem, Cilastatin, and Relebactam; Application to Market Formulations and Biological Fluids; Greenness Assessment.

Abstract

The proposed study introduces a rapid, sensitive, and simple synchronous spectrofluorimetric technique for simultaneous quantification of relebactam, cilastatin, and imipenem in marketed pharmaceutical forms and biological fluids. Using synchronous fluorescence spectroscopy at Δ λ = 110 nm, cilastatin was detected at 360 nm. Fourier Self-Deconvolution was subsequently applied to the spectrum to estimate relebactam and imipenem at 430 nm and 470 nm, respectively after detection of cilastatin at 360 nm ensuring no cross-interference. The pH was adjusted to 8.0 using 2.0 mL of alkaline borate buffer. This approach allowed for the precise quantification of relebactam, cilastatin, and imipenem through ranges of 50-400 ng mL^- 1, 20-500 ng mL^- 1, and 50-500 ng mL^- 1 respectively. The lower detection and quantitation limits were 9.9 and 29.7 ng mL^- 1 for REL, 4.5 and 13.6 ng mL^- 1 for CIL and 5.5 and 16.5 ng mL^- 1 for IMP. The proposed method was successfully applied for the determination of studied drugs in their pharmaceutical formulations with a high degree of accuracy and without interference from common excipients. This approach allowed for the precise quantification of relebactam, cilastatin, and imipenem through ranges of 50-400 ng mL^- 1, 20-500 ng mL^- 1, and 50-500 ng mL^- 1, respectively. The proposed method was rigorously validated according to ICH guidelines. Furthermore, the method's environmental impact was assessed using Eco-scale and Green Analytical Procedure Index (GAPI) techniques.