Validation and clinical application of a multiplex high performance liquid chromatography - tandem mass spectrometry assay for the monitoring of plasma concentrations of 12 antibiotics in patients with severe bacterial infections.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2ABB9B287690
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Validation and clinical application of a multiplex high performance liquid chromatography - tandem mass spectrometry assay for the monitoring of plasma concentrations of 12 antibiotics in patients with severe bacterial infections.
Journal
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Author(s)
Decosterd L.A., Mercier T., Ternon B., Cruchon S., Guignard N., Lahrichi S., Pesse B., Rochat B., Burger R., Lamoth F., Pagani J.L., Eggimann P., Csajka C., Choong E., Buclin T., Widmer N., André P., Marchetti O.
ISSN
1873-376X (Electronic)
ISSN-L
1570-0232
Publication state
Published
Issued date
10/11/2020
Peer-reviewed
Oui
Volume
1157
Pages
122160
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Unpredictable pharmacokinetics of antibiotics in patients with life-threatening bacterial infections is associated with drug under- or overdosing. Therapeutic drug monitoring (TDM) may guide dosing adjustment aimed at maximizing antibacterial efficacy and minimizing toxicity. Rapid and accurate analytical methods are key for real-time TDM. Our objective was to develop a robust high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) for multiplex quantification of plasma concentrations of 12 antibiotics: imipenem/cilastatin, meropenem, ertapenem, cefepime, ceftazidime, ceftriaxone, piperacillin/tazobactam, amoxicillin, flucloxacillin, rifampicin, daptomycin.
A single extraction procedure consisting in methanol plasma protein precipitation and H <sub>2</sub> O dilution was used for all analytes. After chromatographic separation on an Acquity UPLC HSS-T3 2.1 × 50 mm, 1.8 µm (Waters®) column, quantification was performed by electro-spray ionisation-triple quadrupole mass spectrometry with selected reaction monitoring detection. Antibiotics were divided in two pools of calibration according to the frequency of analyses requests in the hospital routine antibiotic TDM program. Stable isotopically-labelled analogues were used as internal standards. A single analytical run lasted less than 9 min.
The method was validated based on FDA recommendations, including assessment of extraction yield (96-113.8%), matrix effects, and analytical recovery (86.3-99.6%). The method was sensitive (lower limits of quantification 0.02-0.5 µg/mL), accurate (intra/inter-assay bias -11.3 to +12.7%) and precise (intra/inter-assay CVs 2.1-11.5%) over the clinically relevant plasma concentration ranges (upper limits of quantification 20-160 µg/mL). The application of the TDM assay was illustrated with clinical cases that highlight the impact on patients' management of an analytical assay providing information with short turn-around time on antibiotic plasma concentration.
This simple, robust high-throughput multiplex HPLC-MS/MS assay for simultaneous quantification of plasma concentrations of 12 daily used antibiotics is optimally suited for clinically efficient real-time TDM.
Keywords
Analytical Chemistry, Clinical Biochemistry, Cell Biology, Biochemistry, General Medicine, Amoxicillin, Analysis, Anti-bacterial agents, Antibacterial, Antibiotics, Assay, Beta-lactams, Carbapenems, Cefepime, Ceftazidime, Ceftriaxone, Cephalosporins, Chromatography, Cilastatin, Concentration, Daptomycin, Ertapenem, Flucloxacillin, Imipenem, Mass spectrometry, Meropenem, Multiplex, Penicillins, Piperacillin, Plasma, Quantification, Rifampicin, Tazobactam, Therapeutic drug monitoring
Pubmed
Web of science
Open Access
Yes
Create date
20/06/2020 22:19
Last modification date
11/11/2020 6:24
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