采用 LC-MS/MS 法测定生物样本中的曲尼司特：在大鼠药代动力学和脑组织分布研究中的应用。

Determination of tranilast in bio-samples by LC-MS/MS: Application to a pharmacokinetic and brain tissue distribution study in rats.

机构信息

Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.

出版信息

J Pharm Biomed Anal. 2018 Jan 5;147:479-484. doi: 10.1016/j.jpba.2017.06.047. Epub 2017 Jun 20.

DOI:10.1016/j.jpba.2017.06.047

PMID:28774678

Abstract

As a potent drug used to improve the neurodegenerative conditions, there is few information about the brain tissue distribution of tranilast by now. In this study, a novel sensitive LC-MS/MS method has been developed and validated to determine tranilast in rat brain tissue samples. The calibration curve showed good linearity ranged from 2.140 to 428.0ng·mL. The method was fully validated and successfully applied in the brain tissue distribution study of tranilast in rats, which had never been reported in detail by now. Furthermore, a rapid LC-MS/MS method with a short run time of 3min was developed and validated for the determination of tranilast in rat plasma and the application to a pharmacokinetic study of tranilast in rats. After oral dosage of 10.5mg·kg tranilast, the maximum plasma concentration (C) of tranilast was (18.59±5.40) μg·mL at (0.667±0.408) h while the area under the curve (AUC) was (54.87±14.13) μg·h·mL with the elimination half-life of (2.93±0.41) h. The ratio calculated by dividing the concentration of tranilast in brain with the concentration of tranilast in the plasma, was (0.6042%±0.0572%), (0.7484%±0.0883%), (0.5914%±0.0416%) and (0.3830%±0.1632%) at 0.167, 0.5, 2 and 8h, respectively. The results showed that tranilast with fast absorption could penetrate the rat brain blood barrier after oral gavage. The obtained data also showed that tranilast could be quickly distributed and eliminated in brain tissue.

摘要

作为一种用于改善神经退行性疾病的有效药物，目前关于曲尼司特在脑组织中的分布信息较少。在本研究中，建立并验证了一种新型灵敏的 LC-MS/MS 方法，用于检测大鼠脑组织样品中的曲尼司特。校准曲线显示出良好的线性范围，为 2.140-428.0ng·mL。该方法经过充分验证，并成功应用于大鼠曲尼司特的脑组织分布研究，这在目前尚未有详细报道。此外，还建立并验证了一种快速 LC-MS/MS 方法，用于测定大鼠血浆中的曲尼司特，该方法的运行时间较短，为 3min，并应用于大鼠曲尼司特的药代动力学研究。大鼠口服 10.5mg·kg 曲尼司特后，曲尼司特的最大血浆浓度（C）为（18.59±5.40）μg·mL，达峰时间（T）为（0.667±0.408）h，曲线下面积（AUC）为（54.87±14.13）μg·h·mL，消除半衰期（T）为（2.93±0.41）h。通过将脑组织中曲尼司特的浓度除以血浆中曲尼司特的浓度计算得出比值，分别为 0.167、0.5、2 和 8h 时的 0.6042%±0.0572%、0.7484%±0.0883%、0.5914%±0.0416%和 0.3830%±0.1632%。结果表明，曲尼司特口服灌胃后能够快速吸收穿透大鼠血脑屏障。获得的数据还表明，曲尼司特能够在脑组织中快速分布和消除。