Tuning and validation of an extraction and chromatography method for omeprazole in drug formulations

Abstract: Gastric ulcer is a common disorder in horses. A known potent inhibitor of gastric acid secretion is omeprazole. This thesis describes the study of omeprazole extraction followed by a high-performance liquid chromatography (HPLC) method for the quantification of omeprazole in enteric-coated pellets (raw material) and in oral paste (final drug product) for horses. The drug product is composed by a paste in which pellets are wrapped. The reason for this investigation is the absence of a proper methodology applicable to the pharmaceutical industry and the necessity to determine the trueness of the method. In the first place, HPLC was validated using a reference standard of omeprazole. The method showed results within acceptable criteria in comparison with the intervals established by the United States Pharmacopeia (USP) for analytical parameters such as linearity (r2=0.9998) and precision (RSD 0.38%). Secondly, the experimental design for the extraction method of omeprazole from pellets was performed by trying a range of extraction conditions, such as the use of magnetic stirring and different sonication times. Extraction of omeprazole method from oral paste was already developed but it needed to be studied deeper. However, when the chromatographic method was applied to raw materials and drug product, higher concentration values than expected were obtained (e.g. 230.66 μg/ml omeprazole in pellets instead of the 220 μg/ml expected). A reason for such high values could be related to systematic errors and the instability of the pellets. Dimensions of pellets, the coating thickness and/or the size of inert core of the pellets can vary and thereby be sources of possible variation. Trueness of the method remains unknown because there is a lack of knowledge about the real concentration value and further studies are needed.