Separation, Identification, and Quantification of N-Acetyl Cilastatin in Human Urine

Abstract

A new high-performance liquid chromatographic method coupled with anion-exchange sample extraction has been developed for the isolation and quantification of N-acetyl cilastatin from human urine samples. N-Acetyl cilastatin, isolated from urine after I.V. administration of cilastatin, was converted to dimethyl esters, and characterized by thin-layer chromatography and mass spectrometry. The detection limit of the assay was 5 μg/ml in urine. The method was shown to be linear, reproducible and reliable for the quantification of N-acetyl cilastatin in urine from four human subjects given I.V. doses of cilastatin alone and together with 250 and 1,000 mg of imipenem.