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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
- 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.
- Subjects :
- Imipenem
Mass spectrometry
Tandem mass spectrometry
High-performance liquid chromatography
Analytical Chemistry
Mice
Tandem Mass Spectrometry
medicine
Animals
Protein precipitation
Enzyme Inhibitors
Spectroscopy
Chromatography
Cilastatin
Chemistry
Hydrophilic interaction chromatography
Organic Chemistry
Imipenem/cilastatin
Haplorhini
Anti-Bacterial Agents
Rats
beta-Lactamase Inhibitors
medicine.drug
Subjects
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