title: Development and validation of a high performance liquid chromatography assay for the determination of temocillin in serum of haemodialysis patients.
abstract: Therapeutic drug monitoring of β-lactams can be useful for the optimization of therapy, especially when little reference data exist on actual pharmacokinetic profiles such as in patients undergoing haemodialysis. There is no reported validated method for temocillin assay in serum samples, and preliminary studies evidenced potential for interferences by acidic metabolites and co-administered drugs in patients with advanced kidney failure. This paper describes a fully validated method for the determination of temocillin in human serum, and its applicability in haemodialysis patients. Temocillin was extracted from human serum by a solid phase extraction methodology, and then assayed by reversed-phase HPLC with UV-detection. The method was validated according to the accuracy profile methodology, using total error to verify the trueness, precision and overall accuracy. It showed high specificity and precision and was accurate in the concentration range of 5-400 mg/L. LOD and LOQ were 1.2 and 5 mg/L, respectively. No interference with 30 co-administered drugs was evidenced. The method was successfully applied to clinical samples from haemodialysis patients, showing a high degree of dialysability of temocillin.
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Miranda Bastos
authors.affiliation: Department Nephrology and Infectious Diseases, AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Vandecasteele
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.affiliation: Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Spinewine
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Center for Clinical Pharmacy, Université catholique de Louvain, Brussels, Belgium. Electronic address: francoise.vanbambeke@uclouvain.be.
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D057230:Limit of Detection; D010406:Penicillins / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000628:therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; C031367:temocillin
keywords: HPLC-UV; Haemodialysis; Temocillin; Therapeutic drug monitoring; Validation