The compensation method and other chemometric methods (derivative, orthogonal function and difference spectrophotometry) have been applied to the direct determination of omeprazole, lansoprazole and pantoprazole in their pharmaceutical preparations. The methods have been validated; the limits of detection were found to be 3.3 x 10(-2), 3.0 x 10(-2) and 3.5 x 10(-2) mug ml(-1) for the three drugs, respectively. The repeatability of the methods were found to be 0.3-0.5%. The linearity ranges were found to be 0.5-3.5 mug ml(-1). The proposed methods have been applied to the determination of the three drugs in their grastro-resistant formulations. The difference spectrophotometric (DeltaA) method is unaffected by the presence of acid induced degradation products; hence can be used as a stability indicating assay. (C) 2002 Published by Elsevier Science B.V.