Identification, Characterization, and Quantification of Impurities of Safinamide Mesilate: Process-Related Impurities and Degradation Products
| Autor: | Liang Zou, Zheying Zhu, Wenkai Hui, Qiaogen Zou, Hui Zhang, Lili Sun |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Benzylamines
Formic acid 01 natural sciences Analytical Chemistry chemistry.chemical_compound Drug Stability Impurity Phase (matter) Environmental Chemistry Acetonitrile Chromatography High Pressure Liquid Mesylates Pharmacology Alanine Chromatography 010405 organic chemistry 010401 analytical chemistry Propanamide 0104 chemical sciences Characterization (materials science) chemistry Scientific method Degradation (geology) Drug Contamination Agronomy and Crop Science Food Science |
| Zdroj: | Journal of AOAC INTERNATIONAL. 100:1029-1037 |
| ISSN: | 1944-7922 1060-3271 |
| DOI: | 10.5740/jaoacint.16-0218 |
| Popis: | The characterization of process-related impurities and degradation products of safinamide mesilate (SAFM) in bulk drug and a stability-indicating HPLC method for the separation and quantification of all the impurities were investigated. Four process-related impurities (Imp-B, Imp-C, Imp-D, and Imp-E) were found in the SAFM bulk drug. Five degradation products (Imp-A, Imp-C, Imp-D, Imp-E, and Imp-F) were observed in SAFM under oxidative conditions. Imp-C, Imp-D, and Imp-E were also degradation products and process-related impurities. Remarkably, one new compound, identified as (S)-2-[4-(3-fluoro-benzyloxy) benzamido] propanamide (i.e., Imp-D), is being reported here as an impurity for the first time. Furthermore, the structures of the aforementioned impurities were characterized and confirmed via IR, NMR, and MS techniques, and the most probable formation mechanisms of all impurities proposed according to the synthesis route. Optimum separation was achieved on an Inertsil ODS-3 column (250 × 4.6 mm, 5 μm), using 0.1% formic acid in water (pH adjusted to 5.0) and acetonitrile as the mobile phase in gradient mode. The proposed method was found to be stability-indicating, precise, linear, accurate, sensitive, and robust for the quantitation of SAFM and its process-related substances, including its degradation products. |
| Databáze: | OpenAIRE |
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