Accelerated Degradation Experiment

Conditions

Appearance of the substance

The substance, originally in the form of a white to greyish white, crystalline powder, changes gradually after procedure A1 into a greyish compact mass, after 2 days into a viscous, yellowish liquid, becoming after procedures A2 and A3 brown and finally black.

Gain of moisture

Chromatographic test

Adsorbent: Silica gel F-254

Solution applied to the plate: Substance dissolved in a 0.2% solution of sodium metabisulfite.

Solvent system:

n-butanol: .............................6 volumes
acetic acid: ...........................2 volumes
water: ...................................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 examined under ultraviolet light at a wavelength of maximum output at about 254 nm, and then examined in white light after exposure to iodine vapours.

Results: Several spots are obtained from the solutions of each of the samples subjected to procedures A1, A2, A3 and B, being more or less mobile than the main spot, when compared to the corresponding spots of the reference solution of epinephrine hydrogen tartrate.

Colorimetric determination

Prepare 0.002% solutions of the samples subjected to procedures A1 and A2 in a 0.5% solution of sodium metabisulfite. Similarly prepare a reference solution of epinephrine hydrogen tartrate.

Transfer to separate test-tubes 1 ml of the solutions to be examined and 1 ml of the reference solution. To each tube add 2 ml of 0.5% sodium metabisulfite solution, 2 ml of water, 1 ml of 0.1% thiosemicarbazide solution and 0.5 ml of 1 N sodium hydroxide. Allow to stand at room temperature for 45 minutes and measure the absorbances at about 480 nm.

After procedure A1: 69%, not including the moisture content of 10-20%, representing a degradation of more than 10%.

Conclusion

Epinephrine hydrogen tartrate is subject to strong decomposition under accelerated degradation conditions.