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Simultaneous quantification of donafenib, sorafenib, and their N-oxide metabolites in rat plasma using a HPLC-MS/MS method.
- Source :
-
Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences . Sep2023, Vol. 1229, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- • The first HPLC-MS/MS method for simultaneous determination of donafenib, donafenib-N-oxide, sorafenib, and sorafenib-N-oxide in rat plasma is developed. • The limited sample volume (50 μL), simple sample preparation (protein precipitation), and short analysis time (2.8 min) are the advantages of the method. • The method is suitable for high-throughput analysis of biological samples. • The method successfully applied to comparing the pharmacokinetic behaviors of the donafenib and sorafenib in rat plasma. Donafenib and sorafenib are small molecule chemotherapy drugs for the management of hepatocellular carcinoma, with donafenib being a deuterated derivative of sorafenib. To date, a high liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that quantify donafenib, sorafenib, and their main metabolites has not yet been developed. The objective of this study was to establish a HPLC-MS/MS method for the simultaneous detection of donafenib, donafenib-N-oxide, sorafenib, and sorafenib-N-oxide and for the pharmacokinetic studies in rat. The extraction of all analytes was achieved by simple protein precipitation utilizing acetonitrile. The Waters XBridge C 18 column (2.1 × 100 mm, 3.5 µm) was selected, and the analytes could be efficiently separated and quantitated during a 2.8 min gradient elution procedure. The method was linear within the predefined quantification ranges and provided acceptable precision (%CV < 9.4%), reproducible extraction recovery (99.4%–111.5%), and low matrix effect (88.1%–98.6%). The hemolysis effect did not interfere with the quantification of all analytes, and similar results were obtained by changing the anticoagulant K 2 -EDTA to heparin or sodium citrate. Plasma pharmacokinetics revealed that the values of t 1/2 , C max , and AUC 0-t of donafenib were 1.4-, 6.2-, and 3.1-fold higher than those of sorafenib, respectively. In conclusion, the proposed bioassay was successfully applied to pharmacokinetic studies in rat after administration of donafenib and sorafenib. Our work not only improves the bioanalytical method for determining the plasma concentrations of donafenib, sorafenib, and their N-oxide metabolites, but also provides a scientific reference for clinical pharmacokinetic studies. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SORAFENIB
*LIQUID chromatography-mass spectrometry
*METABOLITES
*HEPARIN
Subjects
Details
- Language :
- English
- ISSN :
- 15700232
- Volume :
- 1229
- Database :
- Academic Search Index
- Journal :
- Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 173314498
- Full Text :
- https://doi.org/10.1016/j.jchromb.2023.123871