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Abstract: A sensitive and specific high-performance liquid chromatography–tandem mass spectrometry method (LC/ESI/MS) was developed and validated for the identification and quantification of the novel lead compound of anticholinergic drug thiencynonate in rat plasma. The analytes were determined using positive electrospray ionization mass spectrometry in the selected reaction ion monitoring (SRM). The chromatography separation was on BetaBasic-18 column (150mm×2.1mm i.d., 3μm). The mobile phase was composed of methanol–water (70:30, v/v), containing 0.5‰ formic acid, which was pumped at a flow rate of 0.2ml/min. Phencynonate was selected as the internal standard (IS). Simultaneous MS detection of thiencynonate and IS was performed at m/z 364.4 (thiencynonate), m/z 358 (phencynonate), and the SRM of the two compounds were both at 156. Thiencynonate eluted at approximately 2.8min, phencynonate eluted at approximately 2.9min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 1–100ng/ml in rat plasma. The lower limit of quantification (LLOQ) was reproducible at 1ng/ml in rat plasma. The precision measured was obtained from 2.47 to 9.28% in rat plasma. Extraction recoveries were in the range of 67.63–76.76% in plasma. This method was successfully applied to the identification and quantification of thiencynonate in pharmacokinetic studies. [Copyright &y& Elsevier]