Abstract

Background: In order to acquire the best chromatographic condition with maximum resolution and minimum analysis time, the central composite design (CCD) added with Derringer’s desirability function was utilised in order to separation of doripenem, meropenem and ertapenem.

Experiment: The parameters (mobile phase pH values, column temperature and concentration of acetonitrile) affecting separation of these compounds were selected. The first order effects for each factor and their interactions were investigated. Enhanced method was applied correctly for concurrent determination of doripenem, meropenem and ertapenem in human urine, using a X Terra C₁₈ (5 µm, 250 mm x 4,6 mm ID) column. In accordance with ICH guidelines to verify linearity, accuracy and precision.

Result: By using equations obtained CCD, protonation constant values (pK_a) of doripenem, meropenem and ertapenem were also predicted.

Keywords: Carbapenem group, predicted pK_a values, central composite design (CCD), Derringer’s desirability, optimization, RPLC, method validation.

Graphical Abstract