Pharmacokinetic Study of Sulphoxide Prodrug of Famotidine by LC-MS/MS Method in Rabbit Plasma

Abstract

Sulphoxide prodrug of famotidine is a water soluble and biologically inactive derivative of famotidine, a H₂ receptor antagonist to treat ulcer. As the sulphoxide prodrug is a new entity so far no methods has been reported for its estimation in bulk and biological fluids. A rapid liquid chromatography tandem mass spectrometry (LC-MS-MS) method has been optimized for analysis of sulphoxide prodrug of famotidine in rabbit plasma using clopidogrel as internal standard. Following turboionspray ionization, the analytes were quantified on a triple-quadrupole mass spectrometer in multiple-reaction-monitoring positive ion mode. Sample preparation involved a simple one-step protein precipitation with methanol, followed by centrifugation and evaporation of the organic solvent. The residue was re-dissolved in mobile phase and analyzed by LC-MS/MS. A Symmetry C18, 50 × 4.6, 5 μ, a mobile phase composed of acetonitrile: water:triethyl amine:orthophosporic acid (49.9:49.9:0.1:0.1 % v/v/v/v) and a flow rate of 0.6 mL/min were employed and the total run time was 3 min. The method was validated for accuracy, precision, linearity, selectivity, lower limit of quantification (LLOQ), recovery and matrix effect. The method was found to be linear in the range of 15 to 600 ng/mL. Lower limit of quantification was found to be 3.6 ng/mL. All validation parameters met the acceptance criteria according to regulatory guidelines. This method was successfully applied to pharmacokinetic study of the prodrug in rabbit through oral administration.