The recent FDA Biopharmaceutics Classification System (BCS) guidance allows for the use of an acid-base titration method, providing justification is given to support this method to predict equilibrium solubility of the test drug. To evaluate an acid-base titration method compared to the traditional shake-flask method, 30 drugs were selected from the World Health Organization List of Essential Drugs and solubility-pH profiles were determined. The acid-base titration method relies on a characteristic shift in the mid-buffer region of the titration curve when precipitate is present. The shake-flask method consists of 24 hr shaking of saturated solutions, filtration and assaying by UV detection. The drug compounds consisted of acids, bases and ampholytes, with pKa values ranging from 2.0 to 12.0 and log P values ranging from -1.0 to 5.5. Intrinsic solubility values ranging from 0.5 to 20,000 mg/ml were determined by running acid-base titrations over the pH range 1.7 to 12.2. The acid-base titration method proves to be comparable to the shake-flask method for determining solubility-pH profiles and intrinsic solubility values for test drugs.