title: High-performance liquid chromatographic determination of cilastatin in biological fluids.
abstract: Cilastatin, a dehydropeptidase-I inhibitor, is coadministered with the beta-lactam antibiotic imipenem. The described procedure was developed for quantification of cilastatin in human plasma and urine. The assay involved sample purification on a C18 extraction cartridge, reversed-phase high-performance liquid chromatography with post-column derivatization and fluorescence detection. Standard curves were linear from 0.75 to 75.0 micrograms/ml in plasma and from 2.5 to 200.0 micrograms/ml in urine. Intra-day mean coefficients of variation at concentrations within the standard curve range were 4.2 +/- 2.4% and 3.1 +/- 1.7% in plasma and urine, respectively. The inter-day coefficients of variation for analyses of cilastatin in plasma (1.0 and 50.5 micrograms/ml) were less than 10% after 31 days of analysis while those for urine (5.0 and 74.1 micrograms/ml) were less than 11% after 44 days of analysis. The limits of reliable detection were 0.75 and 2.5 micrograms/ml in plasma and urine, respectively. This procedure met the sensitivity and specificity requirements for the analysis of samples from clinical pharmacokinetic studies.
authors.forename: J L
authors.initials: JL
authors.lastname: Demetriades
authors.forename: P R
authors.initials: PR
authors.lastname: Souder
authors.forename: L A
authors.initials: LA
authors.lastname: Entwistle
authors.forename: W C
authors.initials: WC
authors.lastname: Vincek
authors.forename: D G
authors.initials: DG
authors.lastname: Musson
authors.forename: W F
authors.initials: WF
authors.lastname: Bayne
mesh_terms: D002851:Chromatography, High Pressure Liquid; D015377:Cilastatin; D003521:Cyclopropanes / Q000032:analysis* / Q000097:blood / Q000652:urine; D004355:Drug Stability; D006801:Humans
chemical_list: D003521:Cyclopropanes; D015377:Cilastatin