Journal article
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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Decosterd LA
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address: LaurentArthur.Decosterd@chuv.ch.
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Mercier T
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Ternon B
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Cruchon S
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Guignard N
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Lahrichi S
Quantitative Mass Spectrometry Facility, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Pesse B
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Quantitative Mass Spectrometry Facility, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Rochat B
Quantitative Mass Spectrometry Facility, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Burger R
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Lamoth F
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Pagani JL
Adult Intensive Care Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Eggimann P
Adult Intensive Care Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Csajka C
Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
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Choong E
Laboratory of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Buclin T
Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Widmer N
Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; Pharmacy of Eastern Vaud Hospitals, Rennaz, Switzerland.
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André P
Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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Marchetti O
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland.
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Published in:
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. - 2020
English
OBJECTIVE
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.
METHODS
A single extraction procedure consisting in methanol plasma protein precipitation and H2O 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.
RESULTS
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.
CONCLUSION
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.
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Language
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Open access status
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hybrid
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/271785
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