Identification of a drug degradation product found in a stressed dosage form using LC/MSn, LC/TOF MS and on-line H/D exchange MS
| Autor: | Hong Wen, Michael Motto, Changkang Pan, Yanjing Jiang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Dosage Forms
chemistry.chemical_classification Reaction mechanism Magnetic Resonance Spectroscopy Trifluoromethyl Chromatography Spectrophotometry Infrared Carboxylic acid Clinical Biochemistry Pharmaceutical Science Nuclear magnetic resonance spectroscopy Dosage form Analytical Chemistry chemistry.chemical_compound chemistry Deuterium Drug Discovery Nucleophilic substitution Humans Moiety Female Chromatography High Pressure Liquid Spectroscopy |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 57:99-103 |
| ISSN: | 0731-7085 |
| Popis: | An unknown degradation product was found when a dosage form was stressed under base and heat. Comprehensive LC-MS studies have been conducted to identify this degradation product. The approach included the use of an ion-trap MS for MS(n) ion fragmentation patterns, a time-of-flight (TOF) MS to measure the accurate mass for its potential chemical formula, and on-line hydrogen/deuterium (H/D) exchange LC-MS to determine the number of exchangeable hydrogen atoms in the gradation product. Based upon the above LC-MS results, the unknown was identified to result from the conversion of a trifluoromethyl moiety in the drug substance to a carboxylic acid under the combination of thermal and base stress. Different ion fragmentation pathways between the drug substance and its degradation product were discussed. The reaction mechanism was proposed to be nucleophilic substitution through S(N)2 mechanism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect