Chromatography Forum

Could anybody help me understand this?
I am developing a method to test trace amount of polyehtylene oxide in biological matrix(protein and buffer). The company has an old method using size exclusion and RI detector. I searched literature and only spectrophotometric method has been developed (aobut 0.01% Detection limit). I know that size exlusion with RI is for major assay of this polymer. Can it be used for trace analysis?
Thank you in advance.

RI is inherently not very sensitive, and SEC tends to give broad peaks for polymers (based on their MW distribution), so I would think that this would not be a good combination for trace analysis

Maybe an old fashioned ACN, etc., precipitation (proteins) and extraction (polymer), then , for instance, RP-HPLC with UV detection at 200nm? Or, maybe even a restricted access column could work if you are lucky.

Another option to consider which generally exceeds the detection limits of RI is ELSD. In the course of some column development work here, we have been evaluating the capability of our prototype column to separate PEG. We find that ELSD is generally a better option for this class of compounds.