期刊
出版社
ELSEVIER
DOI: 10.1016/j.jchromb.2022.123366
关键词
E7130; Quantitation; Plasma microsampling; High-resolution mass spectrometery (HRMS); Pharmacokinetic study; Selectivity
资金
- Japan Agency for Medical Research and development (AMED) [JP20pc0101051]
This study developed a sensitive analytical method to measure E7130 concentration in mouse plasma samples obtained via microsampling. The UHPLC-HRMS method showed good precision and accuracy in E7130 quantitation, making it a valuable approach for pharmacokinetic analysis and quantitation of compounds.
E7130 is a novel microtubule inhibitor and a promising tumor microenvironment ameliorator. Since the amount of the administration in preclinical study is very small due to the high potency of E7130, this study aimed to establish a sensitive analytical method to measure E7130 concentration in mouse plasma samples obtained via microsampling. A sensitive and validated method was developed based on ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 1.7 mu m (2.1 x 50 mm) column. Mobile phase A comprised 0.1% formic acid and 10 mM ammonium formate in water, and mobile phase B was methanol. A gradient elution was applied at a flow rate of 0.5 mL/min. The calibration curve drawn was linear in the 0.2-100 ng/mL E7130 concentration range for mouse plasma microsamples (10 mu L). Analytical results demonstrated good precision (<6.7%) and accuracy (88.5%-100.0%) in E7130 quantitation, indicating that UHPLC-HRMS is a useful method for pharmacokinetic analysis and a valuable approach for the quantitation of hardly fragmented compounds.
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