[dita]

Hi,

I have a question regarding radicals and oxidation. Is it possible for Triamcinolone acetonide to be an oxidant? Apparently hyaluronic acid has been found to degrade in the presence of triamcinolone acetonide and I am wondering if TA acts as an oxidant.

[orgopete]

This looks like a pretty complicated question. It is not obvious to me how triamcinolone acetonide itself should be an oxidant, but it is also not obvious what the degradation products of hyaluronic acid actually are. What actually happens to hyaluronic acid? Have the degradation products been identified? How is the degradation experiment with triamcinolone acetonide carried out? Could this be a light catalyzed oxygen oxidation?

[dita]

The molecular weight of hyaluronic acid decreases as well as viscosity which is indicative of degradation. Triamcinolone acetonide is suspended in a solution of hyaluronic acid in buffer pH 7.4 and the solution is heated to 80 degrees in an oven. The exposure to light is minimized to avoid light catalyzed oxidation. This is very puzzling for me. I thought maybe TA serves as an oxidant because without TA, the HA under the same condition is fine and doesn't degrade at all.

[orgopete]

Suspended, okay. Is this concentration dependent? Do you recover the triamcinolone acetonide?

[dita]

I tried comparing triamcinolone acetonide to triamcinolone hexacetonide in HA solution and I got similar results to that of a patent that stated that HA didn't degrade in the presence of triamcinolone hexacetonide but did degrade in presence of triamcinolone acetonide.

Yes, I do recover triamcinolone acetonide and the percent recovery is the 98-100%. According to HPLC, triamcinolone acetonide remains the same and there is a small peak representing triamcinolone acetonide 21-aldehyde hydrate (this is expected at high heat). Yes, the concentration is dependent.

Could the aldehyde hydrate form affect HA in someway?

[dita]

The glycosidic bonds are broken hydrolytically and the degradants are sugars:  D-glucuronic acid and D-N-acetylglucosamine

[orgopete]

If the triamcinolone acetonide is recovered, then it isn't being used as an oxidant. I too thought it might have been a hydrolytic reaction, but with the use of a buffer or the absence of the acetonide HA not being consumed, I don't know. There is some subtlety in this that eludes me.