CHEMOMETRIC APPROACH FOR OPTIMIZATION OF HILIC METHOD FOR SIMULTANEOUS DETERMINATION OF IMIPENEM AND CILASTATIN SODIUM IN POWDER FOR INJECTION

Abstract

A new hydrophilic interaction liquid chromatography (HILIC) method was developed for simultaneous determination of imipenem and cilastatin sodium in powder for injection. The proposed method is fast, selective for imipenem and cilastatin sodium in presence of thienamycin (an imipenem degradation product that elutes between the active compounds), and it overcomes the common disadvantages of the ion-pair chromatography. The chemometric approach (Central Composite Face Centered Experimental Design) was used for evaluation of the influence of acetonitrile content, ionic strength of the buffer used in the mobile phase, and column temperature on several chromatographic responses. In this manner, a rational optimization of the method was achieved. The obtained results indicated that the acetonitrile content and ionic strength of the buffer used in the mobile phase had significant effect on the chromatographic behavior of the compounds. The mechanism of retention of imipenem and cilastatin sodium on bare silica column was also investigated. Optimal chromatographic conditions were obtained using Purospher STAR Si column and mixture of ammonium formate (45 mM, pH 5.5) and acetonitrile (32 + 68 v/v) as a mobile phase. The validation results indicated that the proposed HILIC method is suitable for determination of imipenem and cilastatin sodium in powder for injection.