polar analytes due to salts in urine and bile;

apolar analytes due tofat-soluble components in tissues.

LC/MS analysis of a coronary thrombus is the most challenging proteomic analysis I have performed so far.

I think it would be also interesting to write what kind of challenge each sort of sample gives. In blood serum it is the concentration range of proteins of more than 14 orders of magnitude plus a super major protein HSA, plus a dozen other major proteins. So if you want to do anything at all you would have to make (a) depletion, (b) equalization, (c) subfractionation. And whatever you do you would still have a terrible concentration range.