Discoloration

[Apple_insci]

We have a compound in cream formulation. The product (cream) discolored after months sitting in the office. The drug solution discolored after months too. I am analyzing the discolored cream and drug solution using validated stability-indicating method. But no mysterious peak(s) were found. Meanwhile I am doing the forced degradation using HCL, NaOH and H2O2, not degradation peak(s) were found either. I also tried to use multiple wavelenths for detection. NO luck either. I am confused now. What’s more can I try to explain the degradation?

[tom jupille]

A couple of things
- if you haven't already done so, look at a variety of different wavelengths, even out into the visible.
- get hold of a couple of flavors of TLC plates (RP and NP) and do some quick-and-dirty runs. That should give you a general idea how your colored materials behave.
- i'd also do a quick size-exclusion separation, on the chance that whatever your "discolor" comes from is polymeric

[John]

What colour did it turn? You might base your visible detector wavelength upon the colour of the degradent.

Is the discolouration on the surface of the cream only or consistent throughout? This will tell you whether the reaction is caused by air/light or not.

What is the drug?

The impurity may be unretained and therefore be undetected amongst the inj disturbances. It may be stuck to your column and have no mobility in your MP.

JW

[Apple_insci]

The cream turned from white to light yellow. And the color is homogenious. The drug is pretty water-soluable. It shouldn't have retention problem.

The forced degradation by H2O2 showed a bunch of small degradation peaks after alomost 3 days. But I didn't find any trend after comparing the chromatograms of std, original cream, discolored cream, discolored drug solution and peroxide degraded drug solution.

I tried to used different wavelengths from 210nm to 650nm. At 510nm I saw 3 major negative peaks which I know are from slovent and two excipients. Interesting thing is that all discolored solutions and degraded solutions have a very small negative peak next to a major excipient negative peak. Std and Original cream don't. Is it possible that small negative peak is what I am looking for? How can I prove it? and How can I explain the negative peak?

Tom, I am not familar with TLC. Can you explain more about TLC for this kind of study?

Thanks!

[tom jupille]

TLC = Thin-Layer Chromatography

As the name implies, a thin layer (e.g., 0.25 mm) of stationary phase coated on a glass or plastic plate. The sample solution is applied as a small spot (usually 1 cm or so from the bottom edge of the plate). The bottom edge of the plate is placed in a tray of solvent, which migrates upward due to capillarity.

Advantage for your purpose is that you can see where the colored material is going.

A couple of supplier web sites for more information:
http://www.analtech.com/
http://www.camag.com/