Accelerated Degradation Experiment
Conditions
Procedure A1: |
10 days exposure at 50 °C and 100% relative humidity. |
Procedure A2: |
20 days exposure at 50 °C and 100% relative humidity. |
Procedure A3: |
30 days exposure at 50 °C and 100% relative humidity. |
Procedure B: |
30 days exposure at 50 °C and 100% relative humidity followed by 7 days at 70 °C and 100% relative humidity. |
Appearance of the substance
The substance, originally in the form of a white, amorphous or crystalline powder, changes after procedures A1, A2, A3 and B into a liquid that contains an insoluble white matter.
Gain of moisture
Before exposure to heat and humidity: |
0.42% |
After procedure A3: |
35% |
After procedure B: |
39% |
Chromatographic test
Adsorbent: Silica gel F-254
Solution applied to the plate: Substance dissolved in ethane 95%.
Solvent system:
chloroform ............................... 90 volumes
methanol ................................... 20 volumes
concentrated ammonia ................ 1 volume
Development conditions: The solvent is allowed to migrate until the front reaches a line 15 cm from the starting line.
Detection: The plate is examined under ultraviolet light at a wavelength of maximum output at about 254 nm, and then left in a chromatographic chamber containing some iodine crystals until spots appear.
Results: After procedures A and B, three additional spots are detected and the main spot is less intense than the spot corresponding to the reference solution of warfarin sodium.
Ultraviolet spectrophotometry
Prepare a solution containing 1.0 mg of the substance in 100 ml of ethane 95%.
| |
Absorbance at 308 nm |
Before exposure to heat and humidity |
0.375 |
After procedure A1 |
0.350 |
After procedure A2 |
0.300 |
After procedure A3 |
0.288 |
After procedure B |
0.270 |
pH value
Prepare a solution containing 0.1 g of the substance in 10 ml of water.
Before exposure to heat and humidity: |
8.5 |
After procedure B: |
10 |
Conclusion
Warfarin sodium is subject to decomposition under accelerated degradation.
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