Determination of daptomycin in human plasma by liquid chromatography-tandem mass spectrometry. Clinical application.
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.
Biological Pharmacology and Toxicology, University Hospital, Rennes 1 University, Rennes, France.
Marie-Clémence
MC
Verdier
Danièle
D
Bentué-Ferrer
Olivier
O
Tribut
Nicolas
N
Collet
Matthieu
M
Revest
Eric
E
Bellissant
D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017576:Daptomycin / Q000097:blood* / Q000737:chemistry; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D006801:Humans; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy; D013212:Staphylococcus epidermidis; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000900:Anti-Bacterial Agents; D017576:Daptomycin