title: Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography-tandem mass spectrometry method.
abstract: Dalbavancin is a novel second-generation lipoglycopeptide antibiotic with activity against broad range of Gram-positive pathogens. In order to determine the pharmacokinetics (PK) of dalbavancin in pediatric patients, a new High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) bioanalytical method has been developed for quantification of dalbavancin in plasma and in urine. The plasma method was validated for dalbavancin in the linear range from 0.5 μg/mL to 500 μg/mL using 50 μL of K(2) EDTA plasma. For dalbavancin spiked in urine, non-specific binding (NSB) of the drug to polypropylene (PP) urine collection containers was observed. The loss amounted to about 10% per transfer. After successfully establishing the collection/sampling procedure for urine by addition of Triton X-100 to the collection vessels (with a purpose of preventing NSB), the method was validated for dalbavancin in the range from 0.05 μg/mL to 50 μg/mL, using 100 μL of urine. These methods were used to quantify dalbavancin in plasma and urine of hospitalized children in a pediatric dalbavancin PK study. Eighteen percent of the total number of plasma study samples was reassayed for incurred samples reproducibility (ISR) and all the reassayed dalbavancin concentrations were within the ± 20% limits. For urine, all the collected samples were reassayed for ISR and the original dalbavancin concentration was confirmed within the ± 20% limits for 17 (94%) samples; the one remaining urine sample had its reassayed concentration confirmed within ± 25% of the original result.
authors.affiliation: Pfizer Inc., Clinical Pharmacology, 445 Eastern Point Road, Groton, CT 06340 United States. tanja.alebic-kolbah@pfizer.com
authors.forename: Tanja
authors.initials: T
authors.lastname: Alebic-Kolbah
authors.forename: Roger
authors.initials: R
authors.lastname: Demers
authors.forename: Laura
authors.initials: L
authors.lastname: Cojocaru
mesh_terms: D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine
chemical_list: D017334:Teicoplanin; C469289:dalbavancin