Balogh G, Csizér E, Ferenczy G G, Halmos Z, Herényi B, Horváth P, Laukó A, Görög S
Chemical Works of Gedeon Richter Ltd., Budapest, Hungary.
Pharm Res. 1995 Feb;12(2):295-8. doi: 10.1023/a:1016201630774.
We report on a new isomeric impurity of danazol. This impurity designated as isodanazol was detected by reversed-phase high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Its structure was determined after separation by preparative HPLC. Mass spectrometry revealed the isomeric nature of the impurity while the UV spectrum indicated profound difference in the isoxazole moieties. The structure of the isomeric isoxazole ring in isodanazol was determined by NMR spectroscopy using COSY, HETCOR and NOE measurements. The difference between the UV spectra of danazol and isodanazol is explained on the basis of the difference between the aromaticities of their isoxazole rings supported by quantum chemical calculations. The quantitative determination of the impurity down to the 0.05% level can be performed by HPLC, gas chromatography and TLC densitometry.
我们报道了达那唑的一种新的异构体杂质。这种被命名为异达那唑的杂质通过反相高效液相色谱法（HPLC）和薄层色谱法（TLC）检测到。其结构在通过制备型HPLC分离后得以确定。质谱分析揭示了该杂质的异构体性质，而紫外光谱表明异恶唑部分存在显著差异。异达那唑中异构体异恶唑环的结构通过使用COSY、HETCOR和NOE测量的核磁共振光谱法确定。基于量子化学计算支持的它们异恶唑环芳香性的差异，解释了达那唑和异达那唑紫外光谱之间的差异。该杂质低至0.05%水平的定量测定可通过HPLC、气相色谱法和TLC密度测定法进行。
