Quantifying Isotibolone in Raw Materials of Tibolone
- 1 Departamento de Físico-Química, Instituto de Química, Universidade Estadual Paulista, Araraquara, Brazil
- 2 Department of Physics, University of Guelph, Guelph, Canada
- 3 Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil
- 4 Faculty of Pharmaceutical Sciences, Department of Pharmacy, University of S?o Paulo, S?o Paulo, Brazil.
- 5 Departamento de Físico-Química, Instituto de Química, Universidade Estadual Paulista, Araraquara, Brazil
Abstract
Tibolone, a synthetic steroid, is used in the treatment of natural or surgical menopause disturbs resultant of estrogenic deficiency. Isotibolone (Δ 4 -tibolone) is one of the three active metabolic degradation products of tibolone that displays progestagenic effects on carcinoma cell growth and gene regulation. Isotibolone can be present in raw material of tibolone due to some inadequate synthesis or storage. Its presence is necessary to be identified and quantified in active pharmaceutical ingredients (API), before its use in the manufacturing of medicines. After a recent study on the crystal structure determination of isotibolone, quantitative phase analyses of both tibolone and isotibolone in raw materials and tablets became possible to be conducted. X-ray powder diffraction is one recommended tool for this purpose, but it can be highly frustrating due to the extreme peak overlap when conventional laboratory equipments are used. In this work we show that the use of Brazilian Synchrotron Light Source X-ray powder diffraction data and the Rietveld method can be successfully applied to identify and quantify the isotibolone in two samples of tibolone raw materials.
- K. Modelska and S. Cummings, “Clinical Review 140— Tibolone for Postmenopausal Women: Systematic Review of Randomized Trials,” Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 1, 2002, pp. 1623. doi:10.1210/jc.87.1.16
- T. Van Engelgem and J. Marechal, “Pharmaceutical Composition Comprising Cyclodextrin Complex of Tibolone,” Patent No. WO2005084682A1, 2005.
- S. X. M. Boerrigter, C. J. M. van den Hoogenhof, H. Meekes, P. Verwer and P. Bennema, “Pseudomorphic Crystal Growth of the Model Steroid Methyl Analogue of Norethindrone,” Journal of Physical Chemistry B, Vol. 106, No. 51, 2002, pp. 13224-13230. doi:10.1021/jp014416q
- P. H. G. M. Kirchholtes, G. A. J. M. T. Sas, P. H. G. Kirchholtes, G. A. J. M. Sas, M. K. P. Gerard, S. G. A. J. Theresia and S. G. A. J. M. Theresia, “High Purity Composition Comprising (7-Alpha,17alpha)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one,” US Patent No. 6969708B1, 2000.
- “European Pharmacopoeia,” 5th Edition, Supplement 5.7, 2006, pp. 5124-5125.
- S. I. Sampath, V. P. Neelima and S. Raj, “Quantitative Analyses of Complex Pharmaceutical Mixtures by the Rietveld Method,” Powder Diffraction, Vol. 16, No. 1, 2001, pp. 20-24. doi:10.1154/1.1332076
- C. E. Botez, P. W. Stephens, C. Nunes and R. Suryanarayanan, “Crystal Structure of Anhydrous Delta-d-Mannitol,” Powder Diffraction, Vol. 18, No. 3, 2003, pp. 214218. doi:10.1154/1.1582460
- W. Dong, C. Gilmore, G. Barr, C. Dallman, N. Feeder and S. Terry, “A Quick Method for the Quantitative Analysis of Mixtures. 1. Powder X-Ray Diffraction,” Journal of Pharmaceutical Sciences, Vol. 97, No. 6, 2008, pp. 2260-2276. doi:10.1002/jps.21142
- F. F. Ferreira, S. G. Antonio, P. C. P. Rosa and C. D. O. Paiva-Santos, “Crystal Structure Determination of Mebendazole Form a Using High-Resolution Synchrotron X-Ray Powder Diffraction Data,” Journal of Pharmaceutical Sciences, Vol. 99, No. 4, 2010, pp. 1734-1744.
- F. F. Ferreira, A. C. Trindade, S. G. Antonio and C. D. Paiva-Santos, “Crystal Structure of Propylthiouracil Determined Using High-Resolution Synchrotron X-Ray Powder Diffraction,” CrystEngComm, Vol. 13, No. 17, 2011, pp. 5474-5479. doi:10.1039/c1ce05362k
- A. Gomez, S. G. Antonio, G. L. B. Araujo, F. F. Ferreira and C. D. O. Paiva-Santos, “Crystal Structure of Isotibolone: A Major Degradation Product of Tibolone,” CrystEngComm, Vol. 14, No. 8, 2012, pp. 2826-2830. doi:10.1039/c2ce06504e