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Determination of daptomycin in human plasma by liquid chromatography-tandem mass spectrometry. Clinical application

  • Marie-Clémence Verdier , Danièle Bentué-Ferrer EMAIL logo , Olivier Tribut , Nicolas Collet , Matthieu Revest and Eric Bellissant
Published/Copyright: October 20, 2010

Abstract

Background: Daptomycin is a recently developed cyclic lipopeptide antibiotic active against most Gram-positive pathogens including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To optimize treatment efficacy and safety, especially in patients undergoing multiple drug regimens and/or co-morbidities, a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of daptomycin in plasma.

Methods: A C18 column was used for separation, with a mobile phase initially consisting of 0.1% formic acid, water, and acetonitrile (ACN) in a linear gradient from 20% to 70%. After protein precipitation with ACN, the clear upper layer was diluted in water:ACN (50:50, v/v) before injection. Detection was performed using an electrospray ionization technique. MS/MS transitions, monitored in the positive ion mode were m/z 811.1 → m/z 313.1 for daptomycin, and m/z 609.4 → m/z 194.9 for reserpine, used as internal standard.

Results: Elution of daptomycin and reserpine occurred at 4.5 and 3.9 min, respectively. The method was validated over a range of concentrations from 1 mg/L to 120 mg/L. The assay met recommended acceptance criteria: coefficients of variation were <6.3% and <7.4%, and accuracies were between –5.9% and +11.2% and between –3.5% and +3.7%, for intra- and inter-day validations, respectively.

Conclusions: This method appears well-adapted to routine hospital practice for therapeutic drug monitoring of daptomycin considering its time of analysis, range of concentrations measured, precision and accuracy.


Corresponding author: Danièle Bentué-Ferrer, Service de Pharmacologie Biologique – Toxicologie, CHU de Rennes. Hôpital de Pontchaillou, 2, Rue Henri Le Guilloux, 35033 Rennes cedex, France Phone: +33 2 23 23 47 13, Fax: +33 2 23 23 46 05

Received: 2010-4-20
Accepted: 2010-7-12
Published Online: 2010-10-20
Published in Print: 2011-01-01

©2011 by Walter de Gruyter Berlin New York

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