Kinetics and mechanism of solid state imidapril hydrochloride degradation and its degradation impurities identification

• Authors: Katarzyna Regulska , Beata Stanisz
• Languages of publication: EN

Abstracts

EN

A detailed stability testing of solid state imidapril hydrochloride (IMD) was performed and its degradation products were identified. The analysis was conducted according to ICH guidelines Q1A(R2). Pure IMD samples were exposed to stress conditions of elevated temperature and relative humidity (T = 363 K, RH = 76.4%) in order to accelerate degradation. The regular loss of IMD content with time, and the formation of two degradation impurities were observed. The appropriate reaction rate constants k (for IMD degradation and for the formation of product I and II) were calculated using Prout-Tompkins equation. The obtained degradation products were separated and identified by means of LC-MS technique. Based on the obtained m/z values, the masses and the structures of the formed degradation impurities were established. Also IMD degradation scheme was constructed. It was demonstrated that under the applied analytical conditions, IMD degradation follows an autocatalytic reaction model with the rate constant k = (4.764 ± 0.34)×10 −6 s −1 and with the parallel formation of two degradation products: imidaprilat and the diketopiperazine derivative. The obtained experimental results are in agreement with IMD degradation pathways proposed theoretically. [...]

Keywords

EN

Imidapril hydrochloride; Stability in solid state; LC-MS; Degradation impurities

• Publisher: De Gruyter Open
• Journal: Open Chemistry
• Year: 2013
• Volume: 11
• Issue: 5
• Pages: 754-762

Dates

published

1 - 5 - 2013

online

27 - 2 - 2013

Contributors

author

Katarzyna Regulska

author

Beata Stanisz

• Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 60-780, Poznan, Poland

References

• [1] K. Hayashi, K. Nunami, J. Kato, N. Yoneda, M. Kubo, T. Ochiai, R. Ishida, J. Med. Chem. 32, 289 (1989) http://dx.doi.org/10.1021/jm00122a003[Crossref]
• [2] D.M. Robinson, M.P. Curran, K.A. Lyseng-Williamson, Drugs 67, 1359 (2008) http://dx.doi.org/10.2165/00003495-200767090-00008[Crossref]
• [3] M. Matsuoka, S. Horimoto, M. Mabuchi, K. Banno, J. Chromatogr. 581, 65 (1992) http://dx.doi.org/10.1016/0378-4347(92)80448-Y[Crossref]
• [4] Supplement II to the Japanese Pharmacopoeia Fifteenth Edition, October 1st, 2009, Imidapril hydrochloride Monograph
• [5] B. Stanisz, K. Regulska, K. Kolasa, Acta Polon. Pharm. 68, 645 (2011)
• [6] B. Stanisz, K. Regulska, J. Kania, P. Garbacki, Drug Dev. Ind. Pharm. 39, 51 (2013) http://dx.doi.org/10.3109/03639045.2012.657644[Crossref]
• [7] L. Gu, R.G. Strickley, Pharm. Res. 4, 392 (1987) http://dx.doi.org/10.1023/A:1016430211480[Crossref]
• [8] M.L. Cotton, D.W. Wu, E.B. Vadas, Int. J. Pharm. 40, 129 (1987) http://dx.doi.org/10.1016/0378-5173(87)90058-5[Crossref]
• [9] Y. Guo, S.R. Byrn, G. Zografi, J. Pharm. Sci. 89, 128 (2000) http://dx.doi.org/10.1002/(SICI)1520-6017(200001)89:1<128::AID-JPS13>3.0.CO;2-Z[Crossref]
• [10] Draft Guidance for Industry, Stability Testing of Drug Substances and Drug Products (FDA, Rockville, MD, 1998)
• [11] International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for human use, ICH Harmonized Tripartite Guideline; Stability testing of new Drug substances and Products Q1A (R2), Step 5, ICH, Geneva, 2003
• [12] Stability testing of active substances and pharmaceutical products, Working document QAS/06.179, Draft 2.0, 19 April 2006
• [13] W. Zhou, R.K.J. Gilpin, Pharm. Sci. 93, 1545 (2004) http://dx.doi.org/10.1002/jps.20082[Crossref]
• [14] M. Matsuoka, S. Horimoto, M. Mabuchi, K. Banno, J. Chromatogr. 58, 65 (1992) [Crossref]
• [15] K. Yamanaka, S. Morikawa, K. Murata, et. al., J. Pharm. Biomed. Anal. 14, 281 (1996) http://dx.doi.org/10.1016/0731-7085(95)01595-7[Crossref]
• [16] M. Starek, M. Dąbrowska, Cent. Eur. J. Chem. 10, 711 (2012) http://dx.doi.org/10.2478/s11532-012-0029-y[Crossref]
• [17] J. Cielecka-Piontek, A. Lunzer, A. Jelińska, Cent. Eur. J. Chem. 9, 35 (2011) http://dx.doi.org/10.2478/s11532-010-0125-9[Crossref]
• [18] P. Zalewski, J. Cielecka-Piontek, A. Jelińska, Cent. Eur J. Chem. 10, 121 (2012) http://dx.doi.org/10.2478/s11532-011-0112-9[Crossref]
• [19] R. Skibiński, Cent. Eur J. Chem. 10, 232 (2012) http://dx.doi.org/10.2478/s11532-011-0133-4[Crossref]
• [20] L.R. Snyder, J.J. Kirkland, J.L. Glajch (Eds), Practical HPLC Method Development, (Wiley-Interscience, New York, 1988) 402–438
• [21] Validation of analytical procedures, Proceeding of the International Conference of Harmonisation (ICH) (Commission of the European Communities, 2009)
• [22] E. Pawełczyk, T. Hermann, The Fundamentals of stability drugs (PZWL, Warsaw, 2006) (in Polish)

Identifiers

DOI

10.2478/s11532-013-0212-9