ESTIMATION OF IMPURITY PROFILES OF DRUGS AND RELATED MATERIALS .12. ISOLATION AND IDENTIFICATION OF AN ISOMERIC IMPURITY IN DANAZOL

被引：12

作者：

BALOGH, G ^{[1
]}

CSIZER, E ^{[1
]}

FERENCZY, GG ^{[1
]}

HALMOS, Z ^{[1
]}

HERENYI, B ^{[1
]}

HORVATH, P ^{[1
]}

LAUKO, A ^{[1
]}

GOROG, S ^{[1
]}

机构：

[1] CHEM WORKS GEDEON RICHTER LTD,H-1475 BUDAPEST,HUNGARY

来源：

PHARMACEUTICAL RESEARCH | 1995年 / 12卷 / 02期

关键词：

DANAZOL; ISODANAZOL; IMPURITY PROFILING; IDENTIFICATION; ISOLATION; HPLC; NMR SPECTROSCOPY; HPLC-UV;

D O I：

10.1023/A:1016201630774

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report on a new isomeric impurity of danazol. This impurity designated as isodanazol was detected by reversed-phase highperformance 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.

引用

页码：295 / 298

页数：4

共 12 条

[1] THE DETECTION OF DANAZOL AND ITS SIGNIFICANCE IN DOPING ANALYSIS [J].