Hydrophilic interaction chromatography/tandem mass spectrometry for the simultaneous determination of three polar non-structurally related compounds, imipenem, cilastatin and an investigational β-lactamase inhibitor, MK-4698, in biological matrices

A method coupling hydrophilic interaction chromatography (HILIC) with tandem mass spectrometry (MS/MS) has been developed for the simultaneous determination of three polar non‐structurally related compounds – a carbapenem antibiotic, imipenem (IMP), a renal dehydropeptidase inhibitor, cilastatin (CI...

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Bibliographic Details
Published in:Rapid communications in mass spectrometry 2009-07, Vol.23 (14), p.2195-2205
Main Authors: Xu, Yang, Xie, Wei, Miller-Stein, Cynthia M., Woolf, Eric J.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - chemistry
beta-Lactamase Inhibitors
Chromatography - methods
Cilastatin - blood
Cilastatin - chemistry
Enzyme Inhibitors - blood
Enzyme Inhibitors - chemistry
Haplorhini
Imipenem - blood
Imipenem - chemistry
Mice
Rats
Tandem Mass Spectrometry - methods
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Summary:A method coupling hydrophilic interaction chromatography (HILIC) with tandem mass spectrometry (MS/MS) has been developed for the simultaneous determination of three polar non‐structurally related compounds – a carbapenem antibiotic, imipenem (IMP), a renal dehydropeptidase inhibitor, cilastatin (CIL), and an investigational β‐lactamase inhibitor, MK‐4698 (BLI), in rat plasma, monkey plasma and mouse blood. The analytes were extracted through protein precipitation, chromatographed on a Waters Atlantis HILIC column, and detected on a Sciex API4000 mass spectrometer using a Turbo‐Ion Spray ion source in positive ionization mode following multiple‐reaction monitoring (MRM). The assay dynamic range was 0.1–100 µg/mL for IMP, CIL and BLI, respectively, using a total of 20–25 µL biologic samples, and the total HPLC/MS/MS run time was 4 min/injection. The assay was found to be sensitive, selective and reproducible. The challenges, namely, sample stability, blood sample processing, matrix effect in monkey study samples, and dilution re‐assays for the limited mouse blood samples, are resolved and discussed. This technique allowed rapid analysis of polar compounds in biologic matrixes with satisfactory chromatographic retention and increased throughput. Copyright © 2009 John Wiley & Sons, Ltd.
ISSN:0951-4198
1097-0231
DOI:10.1002/rcm.4138