The present study is focused on the development of methodology for testing drug sensitivity to hydrolytic degradation in different pH conditions in solid-state. To test hydrolytic degradations in solid-state, methodology using different silica and silicates with varying pH (3.9–9.7) was developed. Hydrolytic degradations in varying pH conditions of two drugs, bisoprolol and sofosbuvir were examined in solution as well as in solid-state using HPLC. Impurity profiles in solid-state and in solution differed for sofosbuvir. A bisoprolol hydrolytic curve measured in solid-state showed different dependence between pH and degradation than in solution. The main difference between testing the effects of pH on API stability in solution and in solid-state is that different degradation mechanisms are taking place. It was confirmed that degradation mechanisms observed in solid-state testing are much closer to degradation mechanisms observed for solid dosage forms than degradation mechanism observed while using standard method of testing in solution.