Dear Hanieh,

I highly recommend trying to dissolve your silica NP in an alkali solution. NaOH usually works effectively for this purpose. However, it is uncertain whether your drug will remain stable under these conditions.

Dear Rodolfo Debone Piazza

Thank you for your answer. Yes the problem is that the drug is very hydrophobic and does not dissolve completely in NaOH. The silica dissolves but the drug does not transfer to the aqueous phase of NaOH.

I would check its stability if the drug could transfer.

After silica hydrolysis in water and proper neutralization, you could add methanol or ethanol to the system as co-solvent of your drug. DMSO could also work.

Dear Omar Gonzalez-Ortega

Thank you for your answer. Could you explain more how to do netralization? You mean after addition of NaOh, I make the solution neutral by HCl?

Yes, only if drug concentration is gonna be measured using reverse phase chromatography.

Thank you for your answer Omar Gonzalez-Ortega

That was helpful. I just do not know what heppens to the drug when exposed to basic condition.

Dear Hanieh Montaseri

After hydrolysis and neutralization as suggested by Omar, you may also remove your matrix by filtration/centrifugation before dissolving your drug. It can remove any interference from silica during your analysis.

Many concerns, anyway, you can also extract your drug from the silica using an organic solvent. Which one? It will depend on your particular drug and the interaction that it is having with the silica surface.

Thank you Omar Gonzalez-Ortega It is a very good suggestion. I have seen DCM can extract hydrophobic drugs from Silica. My drug is insoluble in most solvents. I will try this appriach though. Thanks again