Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10554457 | Journal of Pharmaceutical and Biomedical Analysis | 2005 | 7 Pages |
Abstract
Unknown impurities were detected in simvastatin substance and tablets at a 0.2% level using the liquid chromatography technique with UV (DAD) detection. The impurity structures were elucidated by a direct hyphenation of liquid chromatograph to high-resolution mass spectrometer with electrospray ionisation interface using solutions of formic acid in water and in acetonitrile as the mobile phase. Peak tracking was performed using the column-switching technique. Accurate mass measurements by quadrupole time-of-flight mass spectrometer equipped with lock-spray provided information about elemental composition of intact molecules and fragments of impurities. Measurement accuracy for precursor ions was around 3Â ppm and for fragment ions between 4 and 13Â ppm. Mass resolving power was around 6500. Deduced molecular formulae for A1, A2 and A3 impurities were C27H44O6, C26H43O6 and C26H41O5, respectively. The structures proposed for all three impurities revealed modifications of simvastatin molecule on the lactone ring. Impurity A1, detected in simvastatin tablets, was identified as ethyl ester, while the impurities A2 and A3, detected in simvastatin substance, were identified as methyl ester and methyl ether of simvastatin. The impurity from tablets was synthesized and its structure confirmed by LC-UV, LC-MS/MS, and NMR techniques.
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Marko VuletiÄ, Mario CindriÄ, Jasna Dogan Koružnjak,