Abstract
A rapid, sensitive and specific high‐performance liquid chromatography‐electrospray ionization mass spectrometry (LC/ESI‐MS) method was developed and validated for the first time to determine the concentration of lafutidine in human plasma. After the addition of diazepam (the internal standard, IS) and 1 M sodium hydroxide solution to 0.5‐ml plasma sample, lafutidine was extracted from plasma with n‐hexane : isopropanol (95 : 5, v/v). The organic layer was evaporated and the residue was redissolved in 200‐µl mobile phase. The analyte was chromatographically separated on a prepacked Shimadzu Shim‐pack VP‐ODS C~18~ column (250 × 2.0 mm i.d.) using a mixture of methanol‐water (20 mM CH~3~COONH~4~) = 80 : 20 (v/v) as mobile phase. Detection was performed on a single quadrupole mass spectrometer using an electrospray ionization interface and the selected‐ion monitoring (SIM) mode. The method showed excellent linearity (r = 0.9993) over the concentration range of 5–400 ng/ml and had good accuracy and precision. The within‐ and between‐batch precisions were within 10% relative standard deviation. The limit of detection was 1 ng/ml. The validated LC/ESI‐MS method has been successfully applied to the bioequivalence study of lafutidine in 24 healthy male Chinese volunteers. Copyright © 2005 John Wiley & Sons, Ltd.