Micellar Organic-solvent free HPLC design of experiment for the determination of Ertapenem and meropenem; assessment using GAPI, AGREE and analytical Eco-scale models

Ertapenem (ERT) and meropenem (MRP) are widely used carbapenem antibiotics. Their synergistic combined double regimen effect has been reported against resistant bacteria. This study proposes a robust analytical method using a mixed-micellar HPLC technique for their simultaneous determination. Central composite design was used to investigate the effects of different chromatographic variables and to improve the separation effi-ciency of MRP and ERT. The ideal mobile phase consisted of sodium lauryl sulfate (25 mM) and Brij-35 (17 mM) mixed in water at pH 2.5, and at elution rate 1.2 mL min-1 using monolithic RP-C18 column Chromolith (R) Performance RP-18e (100 mm x 4.6 mm) at temperature 40 degreesC. The two drugs were separated in <8 min and determined using UV detector at 305 nm. The method demonstrated linearity throughout concentration ranges of 5-100 and 10-100 mu g mL-1 for MRP and ERT, respectively. The results of trueness and precision calculated in terms of percentage recoveries ranged from 97.5 to 100.8 % for both drugs. The method was applied successfully for the determination of the drugs in their marketed formulations. The analytical eco-scale, green analytical procedure index, AGREE, and RBG-12 models were investigated to assess the analytical greenness of proposed methodology against other reported methods. The green analytical procedure index qualitative assessment together with quantitative AGREE and eco-scale calculations demonstrated the superiority of the developed method. A through comparison of up-to-date reported metrics was introduced and discussed.

Automated summary

This study proposes a robust analytical method using a mixed-micellar HPLC technique for the simultaneous determination of ertapenem and meropenem. The method demonstrated linearity and accurate determination of the drugs in their marketed formulations. The proposed methodology was found to be superior in terms of analytical greenness compared to other reported methods.