UV-Vis Analysis of drug released from Polyester

This post is based off of a conversation with a customer. Their details have been removed to protect their confidentiality.

Question:
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1) In order to detect low-release levels of our drug, we're sampling the release medium, vacuum drying it, and resuspending in EtOH to concentrate 10-fold prior to spectral analysis. We've noticed that the spectra from the polymer encapsulations has a slightly different shape than pure drug alone. Do you have any information about EtOH solubility of the polymers (definitely extremely low for some) or their UV absorbance spectra in solution? Our drug has [a series of UV/Vis abs peaks], so we're trying to pick optimal wavelengths for analysis on a per-polymer basis. Rough ideas of which wavelength regions should be avoided for each polymer would be very helpful if you already have that data on file. Otherwise we'll set our student to the task of generating standard curves.
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Answer:
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1.  This is unfortunately a common issue with drug delivery systems.  The high MW polymers have little solubility in ethanol but as they degrade the various oligomers and low MW materials/acid residues that leach out do in fact contribute to UV/Vis abs.  My experience has been that this effect is greater at lower wavelenghts (particularly strong in the 190-250nm) so if you have a few wavelengths to choose from I would suggest the highest wavelength that you can use to avoid this effect as much as possible.  A 100% sure-fire solution to this problem is to measure the drug elution by HPLC which seperates out the polymer oligomers but this method is slower and if you have many samples can be cumbersome.  It's up to you, if you have it available I would suggest 1st HPLC, if not then try to use the highest wavelength you can to avoid the UV/Vis matrix noise.
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