{"paper_id":"3a416065-ed8a-41cf-9247-6c28d20a6eb7","body_text":"Abstract\nWe 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 U V 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.\nSimilar content being viewed by others\nREFERENCES\nS. Görög, G. Balogh, A. Csehi, É. Csizér, M. Gazdag, Zs. Halmos, B. Hegedüs, B. Herényi, P. Horváth, and A. Laukó. Estimation of impurity profiles in drugs and related materials. Part 11. The role of chromatographic and spectroscopic methods in the estimation of side-reactions in drug syntheses. J. Pharm. Biomed. Anal. 11:1219–1226 (1993).\nA. Laukó, É. Csizér, and S. Görög. Analysis of steroids. Part 46. Qualitative and quantitative characterization of bulk cholesterol by gas chromatography and gas chromatography—mass spectrometry. Analyst. 118:609–613 (1993).\nE. Tóth and J. Törley. Process for preparation of steroid 2,3-d isoxazoles. Hungarian Patent 195.506 (1989).\nG. A. Nygard, L. J. Lovett, G. R. Erdmann, and S. K. Wahba Khalil. Analysis of danazol in serum using high-performance liquid chromatography. J. Chromatogr. 415:438–444 (1987).\nW. D. Hooper, G. R. Cannel, and R. G. Dickinson. Sensitive and selective assay of danazol in plasma by high-performance liquid chromatography. J. Chromatogr. Biomed. Appl. 416:347–352 (1987).\nF. Taylor Noggle, C. Randall Clark, and J. DeRuiter. Liquid chromatographic and spectral analysis of the 17-hydroxy anabolic steroids. J. Chromatogr. Sci. 28:162–166 (1990).\nR. T. Sane, M. Chakraborty, V. G. Nayak, and B. L. Chauhan. Determination of danazol in pharmaceutical preparations by liquid chromatography. J. Chromatogr. 358:448–452 (1986).\nThe United States Pharmacopoeia XXII, USP Convention Inc., Rockville, 1990, pp. 379–380.\nK. Ferenczi-Fodor, Z. Végh, and Zs. Pap-Sziklay. Validation of quantitative planar chromatographic analysis of drug substances. 1.: Definitions and practice in TLC. J. Planar Chromatogr. 6:198–203 (1993).\nD. De Boer, E. De Jong, and R. A. A. Maes. Detection of danazol and its significance in doping analysis. J. Anal. Toxicol. 16:14–18 (1992).\nS. A. Lang and Y. Lin. Isoxazoles and their benzo derivatives. In A. R. Katritzky, C. W. Rees, and K. T. Potts (eds.), Comprehensive Heterocyclic Chemistry. Vol. 6. Part 4B. Pergamon Press, Oxford, 1984, pp. 2–11.\nM. J. S. Dewar, E. G. Zoebisch, E. F. Healy, and J. J. P. Stewart. AM1: A new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107:3902–3909 (1985).\nAuthor information\nAuthors and Affiliations\nRights and permissions\nAbout this article\nCite this article\nBalogh, G., Csizér, É., Ferenczy, G.G. et al. Estimation of Impurity Profiles of Drugs and Related Materials. 12. Isolation and Identification of an Isomeric Impurity in Danazol. Pharm Res 12, 295–298 (1995). https://doi.org/10.1023/A:1016201630774\nIssue date:\nDOI: https://doi.org/10.1023/A:1016201630774","source_license":"CC0","license_restricted":false}