Simultaneous determination of sivelestat and its metabolite XW-IMP-A in human plasma using HPLC-MS/MS.
- Author:
Jing WANG
;
Xiao-jian DAI
;
Yi-fan ZHANG
;
Da-fang ZHONG
;
Yu-lin WU
;
Xiao-yan CHEN
- Publication Type:Journal Article
- MeSH:
Chromatography, High Pressure Liquid;
Chromatography, Liquid;
Glycine;
analogs & derivatives;
blood;
Humans;
Inosine Monophosphate;
blood;
Reproducibility of Results;
Sulfonamides;
blood;
Tandem Mass Spectrometry
- From:
Acta Pharmaceutica Sinica
2015;50(10):1318-1323
- CountryChina
- Language:Chinese
-
Abstract:
A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.
