Daptomycin, a cyclic lipopeptide antibiotic with a broad spectrum of activity against Gram-positive bacteria, is also active against multi-resistant bacterial strains, as well as methicillin-resistant S. aureus, vancomycin-resistant enterococci or penicillin-resistant S. pneumoniae. For these reasons it is a viable alternative for the treatment of persisting infections. However, the therapeutic drug monitoring of daptomycin is recommended because the known variability in drug disposition and the severe clinical conditions of patients. Therefore, we developed a simple and fast UV-HPLC method according to FDA guidelines to monitor plasma concentrations of the drug. Briefly, after a liquid-liquid extraction, plasma calibration samples, quality controls and patients’ samples were injected in a HPLC instrument and peaks of daptomycin and gentamicin (internal standard) were resolved by a C18 250 x 4.6 mm, 5 µm stationary phase and peaks were monitored at UV=262 nm. Mobile phase (isocratic flow of 1 mL/min) consisted of acetonitrile-buffer (KH2PO4 20 mM pH=3.2) 46:54, vol/vol. Under these conditions, IS and daptomycin peaked at 4.1 and 5.8 min after injection. Values of limits of detection and quantitation accounted for 1.65 and 5.00 (g/ml), respectively. Values of method linearity (r2) in range 5-100 mg/L were 0.9975 and 0.9956 plasma samples and solvent standard, respectively. Inter- and intra-day variability coefficients were lower than 15%. The comparison with a reference, commercially-available LC-MS/MS method on 122 patient plasma samples returned excellent correlation (r2=0.9474). In conclusion, the present method demonstrated to be reliable and suitable for daptomycin TDM in clinical routine.

A new validated HPLC-UV method for therapeutic monitoring of daptomycin in comparison with reference Mass Spectrometry

Giacomo Luci
Primo
Writing – Review & Editing
;
Romano Danesi;Antonello Di Paolo
Ultimo
2020-01-01

Abstract

Daptomycin, a cyclic lipopeptide antibiotic with a broad spectrum of activity against Gram-positive bacteria, is also active against multi-resistant bacterial strains, as well as methicillin-resistant S. aureus, vancomycin-resistant enterococci or penicillin-resistant S. pneumoniae. For these reasons it is a viable alternative for the treatment of persisting infections. However, the therapeutic drug monitoring of daptomycin is recommended because the known variability in drug disposition and the severe clinical conditions of patients. Therefore, we developed a simple and fast UV-HPLC method according to FDA guidelines to monitor plasma concentrations of the drug. Briefly, after a liquid-liquid extraction, plasma calibration samples, quality controls and patients’ samples were injected in a HPLC instrument and peaks of daptomycin and gentamicin (internal standard) were resolved by a C18 250 x 4.6 mm, 5 µm stationary phase and peaks were monitored at UV=262 nm. Mobile phase (isocratic flow of 1 mL/min) consisted of acetonitrile-buffer (KH2PO4 20 mM pH=3.2) 46:54, vol/vol. Under these conditions, IS and daptomycin peaked at 4.1 and 5.8 min after injection. Values of limits of detection and quantitation accounted for 1.65 and 5.00 (g/ml), respectively. Values of method linearity (r2) in range 5-100 mg/L were 0.9975 and 0.9956 plasma samples and solvent standard, respectively. Inter- and intra-day variability coefficients were lower than 15%. The comparison with a reference, commercially-available LC-MS/MS method on 122 patient plasma samples returned excellent correlation (r2=0.9474). In conclusion, the present method demonstrated to be reliable and suitable for daptomycin TDM in clinical routine.
2020
Luci, Giacomo; Cucchiara, Federico; Ciofi, Laura; Lastella, Marianna; Danesi, Romano; DI PAOLO, Antonello
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1028010
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