Résumé
OBJECTIVE:To establish a method for the concentration determination of isavuconazole in rabbit cornea. METH-ODS:HPLC was performed on column of Waters X-Bridge C18 with mobile phase of 0.2% glacial acetic acid-acetonitrile(49:51, V/V)at flow rate of 0.7 mL/min,column temperature was 40 ℃,detection wavelength was 284 nm,and injection volume was 10μL. Fifteen Japanese white rabbits with big ears were selected,50 μL of 0.2% isavuconazole suspension was dropped into eyes, then every 3 rabbits were executed after 5,15,30,60,90 min of administration and cornea samples were taken respectively. The determination of isavuconazole were determined after treating. RESULTS:The isavuconazole in leaching solution showed good lin-ear range in 0.0312-2.24μg/mL(r2=0.9999);oethod recovery rate was 91.7%-105.6%(RSD≤6.88%,n=5);extraction recov-ery rate was 100.50%-106.10%(RSD≤2.16%,n=3);and RSDs of inter-day(n=3)and intra-day(n=3)precision and stabili-ty(n=5)tests were lower than 10%. CONCLUSIONS:The method shows strong specificity,high accuracy,good reproducibili-ty,and can rapidly and accurately determine the concentration of isavuconazole in rabbit cornea.
Résumé
Isavuconazole is a broad-spectrum triazole antifungal agent, which is administered as a water-soluble prodrug-isavuconazonium sulfate. Recently, its oral and intravenous formulations are available. Isavuconazole inhibits fungal cytochrome P45014DM, thus interferes with the biological function of cell wall formation and plays the antifungal role. In this paper, we summarize the synthetic methods of isavuconazole, water-soluble segments of side chain and isavuconazonium sulfate and evaluate their advantages and disadvantages, which lays a foundation for isavuconazonium sulfate technology development.
Résumé
Isavuconazole is a broad-spectrum triazole antifungal agent,which is administered as a water-soluble prodrug-isa?vuconazonium sulfate. Recently,its oral and intravenous formulations are available. Isavuconazole inhibits fungal cytochrome P45014DM,thus interferes with the biological function of cell wall formation and plays the antifungal role. In this paper ,we summa?rize the synthetic methods of isavuconazole ,water-soluble segments of side chain and isavuconazonium sulfate and evaluate their advantages and disadvantages,which lays a foundation for isavuconazonium sulfate technology development.