I am trying to find a good reverse phase LC method for predisone and predisolone. I am also planning to incubate these compounds in liver microsomes therefore I would also need to separate the metabolites. Any ideas would be appreciated.

Hello Andrea,
I have had limited interaction with these types of compounds in the past and the following method may be old but here it is anyway.
Column:50 mm x 4.6 mm ChromSpher BioMatrix, 5 um, 250 mm x 4.6 mm ChromSpher C18, 5 um
UV: 240nm
Flow: 1.5ml /min
Temp: 35C
Mobile phase: 10mM phosphate buffer pH=7:THF(75:25 v:v)
I hope this is of some use to you.

I have also problemn finding a RP-HPLC method that separates prednisone and prednisolone from plasma. After LL extraction with CH2Cl2:ethylether 2:3, I could not obtain fine peaks, well resolved from endogenous compounds in a run time less than 20 minutes (together with betametazone as IS). I used short and long C18 columns, with water:THF between 80:20 and 90:10, the flow ranged between 1,2-1,8 ml/min.
Any ideas of improuving my method would be appreciated.

We are working on this method right now and will update you shortly. The method is going to be LC/MS compatible and will allow you to do up to 200 direct injections of plasma. For the column description see the following link:

http://www.allsep.com/Technology_DirectPlasmaAnalysis.php

Silsta
If I understand your comment correctly, your peaks did not look normal after the extraction. If this is the case, the problem could be that you injected the organic solvent into the reversed-phase column. If you do this, you will get peak distortion, often fronting. You can evaporate the organic solvent to dryness, and the reconstitute in the THF/water mobile phase (btw, I would have expected that these compounds elute in high organic, not in such a low organic content).
If my last statement is correct, you may also get away with a dilution of the sample with THF/water, followed by a larger injection volume.

Separation of prednisone and prednisolone is not an easy task on C8 or C18 columns.If I remember correctly, some pharmacopoiea mentions 28:72 Water:THF on a 25 cm column. If you inject stronger solvents, peak shape and separation will be destored.
Then there is a method on a perfluorophenyl column, that does seem to work.

Here is silsta
Thank you for the messages.
I could not resolved yet my problem with prednisone, prednisolone. The samples have methanolic content, and I will try to reconstitute with mobile phase. But I am afraid there is also a column problem. Maybe I need a more dedicated column for this.