Development and validation of a liquid chromatographic–tandem mass spectrometric method for the determination of pibutidine in human urine

Abstract

A liquid chromatographic–tandem mass spectrometric method for the rapid quantitative determination of pibutidine, an H 2-receptor antagonist, in human urine has been developed and validated over the concentration range 0.1–25.6 μg ml −1. Urine samples were prepared based on a simple dilution with 0.05% acetic acid, followed by reversed-phase liquid chromatographic separation. Pibutidine and its internal standard ( 2H 10-pibutidine) were ionized using an electrospray ionization interface and detected by tandem mass spectrometry in the selected reaction-monitoring mode. Completed validation demonstrated the method to be robust, accurate, precise and specific for the direct quantification of pibutidine in human urine. This method has enabled investigation of the urinary excretion of pibutidine following oral administration of pibutidine hydrochloride to healthy subjects.