JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Identification of Degradation Products in the Phosphodiesterase (PDE-4) Inhibitor Roflumilast Using High Resolution Mass Spectrometry and Density Functional Theory Calculations
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : Mass Spectrometry Letters
  • Volume 6, Issue 2,  2015, pp.38-42
  • Publisher : Korean Society Mass Spectrometry
  • DOI : 10.5478/MSL.2015.6.2.38
 Title & Authors
Identification of Degradation Products in the Phosphodiesterase (PDE-4) Inhibitor Roflumilast Using High Resolution Mass Spectrometry and Density Functional Theory Calculations
Paul, Saroj Kumar; Dash, Upendra N.;
  PDF(new window)
 Abstract
Roflumilast analogs are a group of drugs which act as selective photodiesterase (PDE-4) inhibitor for the treatment severe chronic pulmonary disease associated with chronic brochnonities. Structural identification of degradation products using high resolution mass spectrometry and theoretical investigation by density functional theory have been successfully carried out on roflumilast to identify four degradation products namely, 3,5-dichloropyridin-4-amine, N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)-3-hydroxy benzamide, N-(3,5-dichloropyridin-4-yl)-3-(cyclopropylmethoxy)-4-(difluoromethoxy) benzamide and 3-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-4-(difluoro methoxy) benzamide, generated in alkali, acidic and oxidative conditions.
 Keywords
Roflumilast;Mass Spectrometry;Degradation products;DFT;
 Language
English
 Cited by
1.
Identification, characterization and in silico ADMET prediction of Roflumilast degradation products, Journal of Pharmaceutical and Biomedical Analysis, 2017, 138, 126  crossref(new windwow)
 References
1.
Beghe, B.; Rabe, K. F.; Fabbri, L. M. American Journal of Respiratory and Critical Care Medicine 2013, 188, 271. crossref(new window)

2.
Giembycz, Mark, A.; Stephen K. F. Drug Design, Development and Therapy 2010, 4,147.

3.
Boland, S.; Alen, J.; Bourin, A.; Castermans, K.; Boumans, N.; Panitti, L.; Vanormelingen, J.; Leysen, D.; Defert, O. Bioorg. Med. Chem. Lett. 2014, http://dx.doi.org/10.1016/j.bmcl.2014.07.016

4.
ICH, International Conference on Harmonization Guidance for Industry, Impurities in New Drug Products Q3B (R2). 2006.

5.
ICH, Stability Testing of New Drug Substances and Products Q1A (R2), International Conference on Harmonization, IFPMA, Geneva. 2003.

6.
ICH, Impurities in New Drug Substances Q3A (R2), International Conference on Harmonization, IFPMA, Geneva. 2006.

7.
Tarek, S. B.; Hytham, M. A.; Mohamed, S. M.; Hoda, G. D.; Mostafa, M. B. Bulletin of Faculty of Pharmacy Cairo University 2014, 5279.

8.
Barhate, V. D.; Deosthalee, P. Indian J. Pharm. Sci. 2010, 72, 401. crossref(new window)

9.
Sun, C.; Lin, Y.; Sun, M.; Wang, D.; Chen, L. Research on Chemical Intermediates 2013, 1.

10.
Zhang, H.; Lin, Y.; Li, Y.; Dong, K.; Chen, L.; Wang, D. Journal of Chemical Research 2014, 38, 507. crossref(new window)

11.
Lin, Y.; Huang, P.; Qi, H.; Chen, L.; Wang, D. Research on Chemical Intermediates 2013,39, 3111. crossref(new window)

12.
Alex, A.; Harvey, S.; Parsons, T.; Pullen, F. S.; Wright, P.; Riley, J. A. Rapid Commun. Mass Spectrom. 2009, 23, 2619. crossref(new window)

13.
Wright, P.; Alex, A.; Nyaruwata1, T.; Parsons, T.; Pullen, F. Rapid Commun. Mass Spectrom. 2010, 24, 1025. crossref(new window)

14.
Wright, P.; Alex, A.; Pullen, F. S. Rapid Commun. Mass Spectrom. 2014, 28, 1127. crossref(new window)