Synthesis, Characterisation and Biological Evaluation of Dalfampridine Genotoxic Impurities

Mythili, A (2018) Synthesis, Characterisation and Biological Evaluation of Dalfampridine Genotoxic Impurities. Masters thesis, J.K.K.Nattraja College of Pharmacy, Komarapalayam.


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From the planned reaction mechanism and chemistry of pyridine nucleus was understood made an attempt to synthesize different pyridine derivatives, that is fampridine genotoxic impurities from waste application of chemical reactions like N-oxidation, Azo formation, N- deoxygenation, selective deoxigenation, Selective diazo Reduction, Nitro to amine reduction of pyridine containing N- oxide, Nitro to amine reduction, Diamide formation. All the targeted molecules synthesized with good yield and high purity. To achieve high purity attention was drawn forwards automated combiflash and it was performed by developing different analytical methods for separation of synthesized genotoxic impurities. The synthesized genotoxic impurities were characterized using hyponated analytical instruments like NMR, LCMS-MS, HPLC Combiflash. The HPLC purity of genotoxic impurities listed below: 1. IMP-DAL 3 - 99.93%, 2. IMP-DAL 6 - 99.70%, 3. IMP-DAL 4 - 99.05%, 4. IMP-DAL 5 - 99.05%, 5. IMP-DAL 7 - 96.62%, 6. IMP-DAL 2 - 94.42%, 7. IMP-DAL 1 - 92.15%. By the above achievement and all the characterization data’s of genotoxic impurities can be used as reference standards in pharmaceutical industry to evaluate the drug substance. Novel produced compounds, assessed for its in-vitro anti-bacterial activity compared to both gram-positive and gram-negative bacteria using the standard drug Gentamycin. It was concluded as IMP-DAL 1, IMP-DAL 2, IMP-DAL 7 exhibited substantial antibacterial activity against its direction Escherichia-coli ˃ Pseudomonas-aeruginosa ˃ Bacillus-subtilis ˃ Staphylococcus-aureus. IMP-DAL 3, IMP-DAL 4, IMP-DAL 5, IMP-DAL 6 showed mild antibacterial activity contrary to gram +ve bacteria and gram -ve bacteria test organisms. 100 μg/ml of synthesized molecules showed more activity compared to other concentrations.

Item Type: Thesis (Masters)
Additional Information: Reg.No 261615205
Uncontrolled Keywords: Dalfampridine Genotoxic Impurities ; Synthesis ; Characterisation ; Biological Evaluation.
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Subramani R
Date Deposited: 28 Jun 2019 02:14
Last Modified: 28 Jun 2019 02:14

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