Accelerated Degradation Experiment

Conditions

Appearance of the substance

The substance, originally in the form of a white or almost white, crystalline powder, changes after procedure A1 into a paste, its consistency resembling honey.

Gain of moisture

Chromatographic test

Adsorbent: Silica gel F-254

Solution applied to the plate: Substance dissolved in methanol.

Solvent system:

ethyl acetate: ........................5 volumes
acetone: ................................2 volumes
water: ...................................1 volume
acetic acid: ...........................2 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 either 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, or sprayed with a solution of 5% phosphomolybdic acid in acetic acid containing 5% sulfuric acid.

Results: The spots obtained from the solutions of each of the samples subjected to procedures A and B and the spots obtained from the reference solution of dexamethasone sodium phosphate display the same chromatographic characteristics of migration and detection. No additional secondary spot can be observed (the starting material shows two weak secondary spots).

Ultraviolet spectrophotometry

The absorbances are measured at a maximum wavelength at about 240.5 nm and calculated with reference to the dried substance.

After procedures A and B: no change is observed.

Colorimetric determination of the carbonyl group in the A-ring

An ethanolic solution of the substance is treated with 4-aminophenazone in the presence of hydrochloric acid, and the absorbance is measured at 380 nm.

No change is observed.

Conclusion

No chemical modification is detected, but the substance is decomposed as seen from the important gain of moisture under accelerated degradation conditions.