title: Rapid and sensitive LC-MS/MS method for the analysis of antibiotic linezolid on dried blood spot.
abstract: Linezolid is a new drug from the oxazolidinone class of antibiotics used against mycobacteria and multi-drug resistant (MDR) Gram-positive bacterial infections, which may are also glycopeptide-resistant. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate linezolid levels during treatment. Advantages of DBS include short collection time, low invasiveness, ease and low cost of sample collection, transport and storage. The analysis was performed in LC-MS/MS operating in positive ion mode and multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 1-100 mg/L with correlation coefficient value of 0.9987. Intraday and interday coefficients of variation were within 3.6% and 13.0%, respectively. We also tested the thermal and temporal drug stability in dried blood spots at four different temperatures to evaluate the risks of sample delivery in different conditions. The short term stability studies showed that linezolid concentration remained stable for at least one month under all the conditions tested. This new assay has favorable characteristics being highly precise and accurate and allows a fast linezolid analysis with a total run time 22 min long, in gradient analysis. Concentration data for plasma and DBS samples from patients after treatment were compared showing a good correlation. Correlation between DBS data and serum samples measured by HPLC-UV was satisfactory. The benefit for patients is the ability to monitor the treatment with a simple and convenient sample collection at home.
authors.affiliation: Mass Spectrometry Laboratory, Clinic of Pediatric Neurology, A. Meyer Children's Hospital, Florence, Italy. g.lamarca@meyer.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Fabio
authors.initials: F
authors.lastname: Villanelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Daniela
authors.initials: D
authors.lastname: Ombrone
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.forename: Marina
authors.initials: M
authors.lastname: De Gaudio
authors.forename: Stefania
authors.initials: S
authors.lastname: Fallani
authors.forename: Maria Iris
authors.initials: MI
authors.lastname: Cassetta
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelli
authors.forename: Elena
authors.initials: E
authors.lastname: Chiappini
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Martino
authors.forename: Luisa
authors.initials: L
authors.lastname: Galli
mesh_terms: D000081:Acetamides / Q000097:blood*; D000890:Anti-Infective Agents / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D000069349:Linezolid; D023303:Oxazolidinones / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid