Chromatography Forum

In the past I have investigated drug/polymer delivery products, where the drug and polymer are both water insoluable. I found it very difficult to extract the drug from these samples. I could dissolve the drug/polymer in solvents such as dmso, thf or dcm. However, injecting the sample into the HPLC when using a 50/50 sovlent/water mobile phase seems to not be very efficient because the polymer could easily precipitate inside the column. I also tried using a GPC column. The problem with GPC was that the drug has a uv peak around 230nm, so that most of the solvent I would want to use have problems with uv cutoff. THF was borderline, but then there were problems with degradation of the THF.

Are there some methods that I could try in order to extract the drug from the drug/polymer solution? I tried some normal phase SPE without much luck, the recovery of the drug was poor. I looked into LLE but was unable to identify two solvents that were immiscible which also provided solubility for both the drug and polymer (ie every solvent that dissovled the drug was miscible with the solvents that would disolve the polymer).

thanks

GPC looks like a good way to solve the problem. For setting up a GPC method, you could use a different detector than a UV detector. Once you have set up the method, you will never have to worry about it again, since the only shft in retention in true GPC is due to problems with the flow rate. Once the method is established, you could then always clean up your sample blindly, i.e without detector, just as you do with SPE.

You can try seconary dilution of your sample with some simple diluent (acetonitrile buffer mixture or alcohol buffer mixture). The salts in the diluent can help to precipitate the polymer in your sample. Fiter the PPT out before injection.

You can use water as your MP for GPC as long as your drug has considerable solubility in it. If you drug can be seperated with the polymer with any kind of column, the quantitation will be easy.