Accelerated Degradation Experiment

Conditions

Appearance of the substance

The substance, originally in the form of a white to very pale yellow powder changes after procedure A into a pale yellow liquid and upon cooling turning into a heterogenous pale yellow liquid. After procedure B the colour turns to ochre yellow.

Gain of moisture

After procedures A and B: about 50%

Chromatographic test

Adsorbent: Silica gel 60 F-254

Solution applied to the plate: Substance dissolved in methanol.

Solvent system:

chloroform: ............................6 volumes
methanol: ...............................4 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, and then sprayed successively with a solution of titanium trichloride, and with dimethylaminobenzaldehyde or dimethylaminocinnamaldehyde dissolved in diluted hydrochloric acid. The plate is examined at about 365 nm.

Results: The reference solution of chloramphenicol sodium succinate shows two main spots corresponding to the two isomers of esterification in positions 1 and 3, as well as a weak spot corresponding to chloramphenicol. The solutions of each of the samples subjected to procedures A and B show diminished main spots and three additional spots. The spot corresponding to chloramphenicol increases first and diminishes gradually.

Ultraviolet spectrophotometry

Aqueous solutions of the samples subjected to procedures A and B show no modification of the absorption wavelength but the absorbances increase with time.

Gas-liquid chromatography

After procedures A and B, the peaks corresponding to the 2 isomers decrease considerably due to the hydrolysis of the ester; the formed chloramphenicol degrades and several degradation products appear as separate peaks.

Conclusion

Chloramphenicol sodium succinate is subject to decomposition under accelerated degradation conditions.