A Rapid, Validated RP-HPLC Method for the Simultaneous Determination of Cleaning Validation and Cross-Contamination of 12 Beta-Lactam Compounds

Sci Pharm. 2013 Jan-Mar;81(1):151-65. doi: 10.3797/scipharm.1208-20. Epub 2012 Nov 17.

Abstract

The present work reports a rapid reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous determination of 12 beta-lactam components for cleaning validation and cross-contamination. A strategic experimental approach was implemented for the method development. The desired chromatographic separation was achieved on a Symmetry C18 (4.6 X 75 mm, 3.5 μm) column using gradient elution. The optimized mobile phase consisted of the buffer tetrabutylammonium hydroxide pH-6.8 and acetonitrile. The eluted compounds were monitored at 215 nm and 254 nm wavelength using a photodiode array detector. The developed method separated 12-beta-lactam compounds from each other within a run time of 50 min. The method is effective for the determination of cross-contamination of penicillin and cephalosporin production blocks. The present method is specific and a lower limit of quantification was determined on the basis of the signal-to-noise ratio method; it is 1 μg/mL for all components. The developed RP-HPLC method was validated according to the International Conference on Harmonization (ICH) guidelines.

Keywords: Cephalosporin; Chromatography; Cleaning validation; Cross contamination; HPLC; Penicillin.