1. Development and validation of ultra-performance liquid chromatography-tandem mass spectrometric methods for simultaneous and rapid determination of contezolid and its major metabolite M2 in plasma and urine samples and its application to a study in subjects with moderate liver impairment.
- Author
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Wang Y, Wu H, Wu J, Fan Y, Liu X, Li Y, Hu J, Zhang J, and Guo B
- Subjects
- Administration, Oral, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacokinetics, Humans, Limit of Detection, Liquid-Liquid Extraction, Liver Diseases blood, Liver Diseases urine, Oxazolidinones administration & dosage, Oxazolidinones pharmacokinetics, Plasma chemistry, Pyridones administration & dosage, Pyridones pharmacokinetics, Urine chemistry, Anti-Bacterial Agents blood, Anti-Bacterial Agents urine, Chromatography, High Pressure Liquid methods, Liver Diseases drug therapy, Oxazolidinones blood, Oxazolidinones urine, Pyridones blood, Pyridones urine, Tandem Mass Spectrometry methods
- Abstract
Contezolid is a novel oxazolidinone antibiotic with good antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus. For the purpose to further characterize the pharmacokinetics of contezolid and its major metabolite M2, accurate and rapid ultra-performance liquid chromatography-tandem mass spectrometric assays (UPLC-MS/MS) were developed and validated for simultaneous quantification of contezolid and M2 in human plasma and urine. The plasma samples were pretreated by liquid-liquid extraction. The automated solid phase extraction method was used to preprocess urine samples. ACQUITY UPLC® BEH C8 (2.1 mm × 100 mm, 1.7 µm) column was used to separate the analytes with a gradient mobile phase of acetonitrile and water at a flow rate of 0.4 mL/min. The calibration curves showed good linearity over the concentration ranges of 0.0100-5.00 µg/mL for contezolid in plasma and urine, 0.00200-1.00 µg/mL in plasma and 0.0200-10.0 µg/mL in urine for M2, respectively. For both plasma and urine assays, the intra- and inter-batch accuracy and precision were within 15% for all quality control levels, including the lower limit of quantitation. The methods were fully validated and successfully applied to a pharmacokinetic study of contezolid tablets in subjects with moderate hepatic impairment., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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