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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

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

Authors :
Eric Woolf
W. Xie
Yang Xu
Cynthia Miller-Stein
Source :
Rapid Communications in Mass Spectrometry. 23:2195-2205
Publication Year :
2009
Publisher :
Wiley, 2009.

Abstract

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 beta-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 microg/mL for IMP, CIL and BLI, respectively, using a total of 20-25 microL 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.

Details

ISSN :
09514198
Volume :
23
Database :
OpenAIRE
Journal :
Rapid Communications in Mass Spectrometry
Accession number :
edsair.doi.dedup.....74413e62080560d4f23bf693b0cc8d1c
Full Text :
https://doi.org/10.1002/rcm.4138