title: Determination of thiencynonate by liquid chromatographic-mass spectrometry and its application to pharmacokinetics in rats.
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 (150 mm x 2.1 mm i.d., 3 microm). The mobile phase was composed of methanol-water (70:30, v/v), containing 0.5 per thousand formic acid, which was pumped at a flow rate of 0.2 ml/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 2.8 min, phencynonate eluted at approximately 2.9 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 1-100 ng/ml in rat plasma. The lower limit of quantification (LLOQ) was reproducible at 1 ng/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.
authors.affiliation: Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital University of Medical Sciences, Beijing 100069, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuying
authors.initials: Y
authors.lastname: Kou
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Ruan
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D002138:Calibration; D018680:Cholinergic Antagonists / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013876:Thiophenes / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018680:Cholinergic Antagonists; C516245:N-methyl-9-(3-azabicyclo(3.3.1)nonanyl)-2'-cyclopentyl-2'-hydroxy-2'-thienylacetate; D013876:Thiophenes