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- W2460117423 abstract "For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100 μL sample with 400 μL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2 μL processed sample was injected onto an Accucore C-18 column (2.6 μm, 100 × 2.1 mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302 nm allowed quantification limits of 0.5, 2 and 0.5 μg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14 min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24 h compared to t = 0 in CaMHB at 37 °C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising." @default.
- W2460117423 created "2016-07-22" @default.
- W2460117423 creator A5080659713 @default.
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- W2460117423 date "2016-08-01" @default.
- W2460117423 modified "2023-10-18" @default.
- W2460117423 title "Simultaneous determination and stability studies of linezolid, meropenem and vancomycin in bacterial growth medium by high-performance liquid chromatography" @default.
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- W2460117423 doi "https://doi.org/10.1016/j.jchromb.2016.06.033" @default.
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