Your problem appears to be that of pH. C18 may not be ok. Some suggestions is possible if you give more chemistry of your compound. I Had similar problem with one of my compound. When I deleted DMSO as injection solvent or peek fittings from HPLC system the problem was solved. But I am not getting a linear response.
Retention time is stable but areas are going here and there.
I will first look into the pH effect on the solubility of your drug. I am suggesting the following generic method give it a try. I am assuming you are attempting in plasma. Irreproducible peak shape is due to poor recovery. Playing around with pH and little up front work will help the over all performance of your assay method.