Accelerated Degradation Experiment

Conditions

Appearance of the substance

The substance, originally in the form of a white or faintly yellowish, crystalline powder, changes after procedure A1 into a dark blue, viscous solution, and after procedures A2 and B the colour is intensified.

Gain of moisture

After procedures A1, A2 and B: 55%

Chromatographic test

Adsorbent: Silica gel F-254

Solution applied to the plate: Substance dissolved in ethane 95%.

Solvent system:

concentrated ammonia .......... 1.5 volumes
methanol ............................... 100 volumes

Development conditions: The solvent is allowed to migrate until the front reaches a line 15 cm from the starting line.

Detection: The plate is left in a chromatographic chamber containing some iodine crystals until spots appear.

Results: The spots obtained from the solution of the sample subjected to procedure A1 and the spots obtained from the reference solution of promethazine hydrochloride display the same chromatographic characteristics of migration and detection. Beside the main spot a more mobile spot is observed. After procedure A2, two secondary spots are obtained, one is more mobile than the main spot. The degradation was assessed at less than 5%. After procedure B, the intensity of the two secondary spots was increased. The degradation was assessed at about 5%.

Conclusion

Promethazine hydrochloride is subject to decomposition under accelerated degradation conditions. The blue colour assumed by the substance is a very sensitive indicator to test for gross degradation.