Bioanalytical Method Development and Validation of Esomeprazole in Human Plasma by Lc-Ms/Ms.

Abstract

This studies to measure Bioavailability and/or establish Bioequivalence of a product are important elements in support of orally administered drug products in investigational new drug applications (INDs), new drug applications (NDAs) , abbreviated new drug applications (ANDAs), and their supplements. The systemic exposure profile determined during clinical trials in the IND period can serve as a benchmark for subsequent BE studies. Until recently, bioavailability (rate and extent of absorption of medicaments from drug delivery systems) of drugs was not emphasized. It was more or less assumed that if the physical and chemical integrities of a drug product were assured pharmacologic performance would be observed. It is now recognized that formulation factors can influence the biologic availability of a medicament from a dosage unit in mammalian systems. Consequently, it has become common practice to establish bioavailability by measurement of blood levels of drugs following administration of dosage forms. However, it should be noted that either bioavailability or bioequivalence data could be generated without analytical methodology to accurately measure drugs in biological fluids. Currently there is a need in the pharmaceutical environment to develop analytical methods for the determination of Esomeprazole in human plasma. The developed method could then be applied to clinical trials to obtain accurate pharmacokinetic parameters in human plasma. HPLC-UV and LC-MS/MS methods have been reported. Some of these methods use complicated extraction equipments, long and tedious extraction procedures, and large amounts of solvents or biological fluids for extraction while other methods have a long turn around time during analysis. Esomeprazole is a proton pump inhibitor which reduces gastric acid secretion through inhibition of H+/K+-ATPase in gastric parietal cells. By inhibiting the functioning of this enzyme, the drug prevents formation of gastric acid. The bioanalytical methodology described in this manuscript was specific, sensitive, accurate and precise. The method employed HPLC coupled with electrospray ionization mass spectrometric detection (LC-ESI-MS). The method involved a simple sample preparation by liquid- liquid extraction followed by isocratic chromatographic separations. A sensitive method that is precise and accurate over a linear assay range of 5.000 – 1000.000 ng/mL has been validated for the determination of Esomeprazole in Human plasma using LC-MS/MS Method. The LC-ESI-MS method was capable of estimating 5 ng/ml of Esomeprazole accurately in human plasma with high degree of reproducibility.The method can be useful for further BA/BE studies Pharmacokinetic studies