Accelerated Degradation Experiment

Conditions

Appearance of the substance

The substance, originally in the form of a white to yellowish, crystalline powder, changes after procedures A1, A2 and B into an increasingly yellow-coloured powder and becoming more and more deliquescent.

Gain of moisture

Chromatographic test

Adsorbent: Silica gel F-254

Solution applied to the plate: Substance dissolved in methanol.

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 examined under ultraviolet light at a wavelength of maximum output at about 254 nm.

Results: The spots obtained from the solution of the sample subjected to procedure A1 compared to the spots obtained from the. reference solution of procarbazine hydrochloride are more numerous and their intensities are increased after procedures A2 and B.

Ultraviolet spectrophotometry

Absorbances measured at about 232 nm of a solution in ethane 95%.

A second maximum at about 314 nm appears after procedure A1, the absorbance of which increases after procedures A2 and B.

Potentiometric determination

An acidimetric determination in aqueous solution shows a significant decrease of the content from 94 to 55% after procedures A1 and B.

Colorimetric determination

To aqueous solutions of the samples subjected to procedures A1 and B, add pyrocatechol in acetone, followed by silver oxide. The absorbance is measured at about 510 nm.

A decrease in absorbance is observed showing a degradation ranging from 6 to 46%.

Solubility

The substance, originally freely soluble in water, soluble in methanol and ethane 95% shows a decrease in solubility after procedures A1, A2 and B.

Conclusion

Procarbazine hydrochloride is subject to strong decomposition under accelerated degradation conditions.