title: Therapeutic drug monitoring of cefepime with micellar electrokinetic capillary chromatography: Assay improvement, quality assurance, and impact on patient drug levels.
abstract: The improvement and performance of a micellar electrokinetic capillary chromatography assay for cefepime in human serum and plasma with a 50 μm id fused-silica capillary elongated from 40 to 60 cm is reported. Sample preparation with dodecylsulfate protein precipitation at pH 4.5, the pH 9.1 separation medium, and the applied voltage were as reported previously [16]. The change resulted in a significant lower current, higher resolution, and increased detection time intervals. The performance of the assay with multilevel internal calibration was assessed with calibration and control samples. Quality assurance data of a 2-year period assessed under the new conditions demonstrated the robustness of the assay. In serum samples of patients who received both cefepime and sulfamethoxazole, cefepime could not be detected due to the inseparability of the two compounds. The presence of an interference can be recognized by an increased peak width (width > 0.2 min), the appearance of a shoulder or an unresolved double peak. The patient data gathered during a 3-year period reveal that introduction of therapeutic drug monitoring led to a 50% reduction of the median drug level. The data suggest that therapeutic drug monitoring can help to minimize the risk of major adverse reactions and to increase drug safety on an individual basis.
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Regula
authors.initials: R
authors.lastname: Theurillat
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Jeannine
authors.initials: J
authors.lastname: Joneli
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wanzenried
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Schiess
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Hurni
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.affiliation: Department of Infectious Diseases, University Hospital of Bern and Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Parham
authors.initials: P
authors.lastname: Sendi
authors.affiliation: Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
mesh_terms: D000077723:Cefepime; D002511:Cephalosporins / Q000032:analysis*; D020374:Chromatography, Micellar Electrokinetic Capillary; D016903:Drug Monitoring; D006801:Humans; D015394:Molecular Structure; D058996:Quality Improvement
chemical_list: D002511:Cephalosporins; D000077723:Cefepime
keywords: Capillary electrophoresis; Cefepime; Micellar electrokinetic capillary chromatography; Therapeutic drug monitoring