Sayre Casey L, Takemoto Jody K, Martinez Stephanie E, Davies Neal M
Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T5.
Biomed Chromatogr. 2013 Jun;27(6):681-4. doi: 10.1002/bmc.2853. Epub 2012 Dec 5.
An analytical method enabling the detection and quantification of the individual enantiomers of racemic (±) pinocembrin is required to fully characterize its pharmacokinetic disposition. Direct resolution of the enantiomers of pinocembrin was achieved using a novel and simple reversed-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry in rat serum. A Chiralcel® AD-RH column was employed to perform baseline separation with electrospray positive-mode ionization with selected ion monitoring detection. The standard curves were linear from 0.5 to 100 µg/mL for each enantiomer. The limit of quantification was 0.5 µg/mL. The assay was applied successfully to stereoselective serum disposition of pinocembrin enantiomers in rats. Pinocembrin enantiomers were detected in serum. Both enantiomers had a serum half-life of ~15 min in rats. Similar values of volume of distribution between the enantiomers were also observed: 1.76 L/kg for S-pinocembrin and 1.79 L/kg for R-pinocembrin. Total clearance was 5.527 L//h/kg for S-pinocembrin and 5.535 L/h/kg for R-pinocembrin, and the area under the curve was 1.821 µg h/mL for S-pinocembrin and 1.876 µg h/mL for R-pinocembrin. The large volume of distribution coupled with the short serum half-life suggests extensive distribution of pinocembrin into the tissues.
为了全面表征外消旋（±）松属素的药代动力学特征，需要一种能够检测和定量其对映体的分析方法。采用一种新颖且简单的反相高效液相色谱法，结合电喷雾电离和大鼠血清质谱检测，实现了松属素对映体的直接拆分。使用Chiralcel® AD-RH柱进行基线分离，采用电喷雾正模式电离和选择离子监测检测。每种对映体的标准曲线在0.5至100 µg/mL范围内呈线性。定量限为0.5 µg/mL。该方法成功应用于大鼠体内松属素对映体的立体选择性血清处置研究。在血清中检测到了松属素对映体。两种对映体在大鼠体内的血清半衰期均约为15分钟。对映体之间的分布容积值也相似：S-松属素为1.76 L/kg，R-松属素为1.79 L/kg。S-松属素的总清除率为5.527 L/h/kg，R-松属素为5.535 L/h/kg，S-松属素的曲线下面积为1.821 µg·h/mL，R-松属素为1.876 µg·h/mL。分布容积大且血清半衰期短表明松属素在组织中广泛分布。
