Original Paper

Analytical and Bioanalytical Chemistry

, Volume 405, Issue 10, pp 3215-3231

LC-MS/TOF, LC-MSn, on-line H/D exchange and LC-NMR studies on rosuvastatin degradation and in silico determination of toxicity of its degradation products: a comprehensive approach during drug development

  • Ravi P. ShahAffiliated withDepartment of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER)Biocon Bristol-Myers Squibb R&D Centre (BBRC)
  • , Archana SahuAffiliated withDepartment of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER)
  • , Saranjit SinghAffiliated withDepartment of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER) Email author 

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Abstract

The present study dealt with the forced degradation behaviour of rosuvastatin under ICH prescribed stress conditions. The drug was found to be labile under acid hydrolytic and photolytic conditions, while it was stable to base/neutral hydrolytic, oxidative and thermal stress. In total, 11 degradation products were formed, which were separated on a C-18 column using a stability-indicating method. LC-MS analyses indicated that five degradation products had the same molecular mass as that of the drug, while the remaining six had 18 Da less than the drug. Structure elucidation of all the degradation products was executed using sophisticated and modern structural characterization tools, viz. LC-MS/TOF, LC-MSn, on-line H/D exchange and LC-NMR. The degradation pathway and mechanisms of degradation of the drug were delineated. Additionally, in silico toxicity was predicted for all the degradation products using TOPKAT and DEREK software and compared with the drug. This study demonstrates a comprehensive approach of degradation studies during the drug development phase.

http://static-content.springer.com/image/art%3A10.1007%2Fs00216-013-6760-1/MediaObjects/216_2013_6760_Figa_HTML.gif
Figure

Degradation pathway of rosuvastatin

Keywords

Rosuvastatin Stress studies Degradation product LC-MS/TOF MSn studies LC-NMR