色谱

色谱 ›› 2019, Vol. 37 ›› Issue (12): 1291-1296.DOI: 10.3724/SP.J.1123.2019.05026

• 研究论文 • 上一篇    下一篇

超高效液相色谱-串联质谱法测定人血浆中苯海索

杨雨菲1, 夏云燕2, 吴莎1, 邹巧根2   

  1. 1.南京工业大学生物与制药工程学院, 江苏 南京 211816;
    2.南京工业大学药学院, 江苏 南京 211816
  • 收稿日期:2019-06-14 出版日期:2019-12-08 发布日期:2020-12-11
  • 通讯作者: 邹巧根.Tel:(025)83206648,E-mail:qiaogenzou@hotmail.com.

Determination of trihexyphenidyl in human plasma by ultra high performance liquid chromatography-tandem mass spectrometry

YANG Yufei1, XIA Yunyan2, WU Sha1, ZOU Qiaogen2   

  1. 1. College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China;
    2. School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, China
  • Received:2019-06-14 Online:2019-12-08 Published:2020-12-11

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摘要： 建立了灵敏、高通量的超高效液相色谱-串联质谱（UPLC-MS/MS）定量测定人血浆中苯海索的方法，用于盐酸苯海索片生物等效性研究，并确证食物对苯海索体内药代动力学行为的影响。以甲醇为沉淀剂进行蛋白质沉淀，苯海索-d11为内标，采用Waters Acquity UPLC BEH C8色谱柱（50 mm×2.1mm，1.7 μm），以0.1%（v/v）甲酸水溶液（含5 mmol/L醋酸铵）和乙腈-水（95：5，v/v）为流动相进行梯度洗脱；采用电喷雾电离（ESI）源，在正离子模式下进行多反应监测（MRM）扫描。苯海索在0.1~40 ng/mL范围内线性关系良好。应用该方法测定中国健康受试者空腹及餐后单次口服2 mg盐酸苯海索片后的血药浓度，结果显示最大血药浓度（Cmax）、血药浓度-时间曲线下面积（AUC0-t、AUC0-∞）的90%置信区间均在80.0%~125.0%范围内，表明两种制剂在空腹和餐后均生物等效。

关键词: 超高效液相色谱-串联质谱, 人体药代动力学, 生物等效性, 苯海索

Abstract: A sensitive and high throughput method by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the determination of trihexyphenidyl in human plasma. The method was used to evaluate the bioequivalence of the test preparation and reference preparation, and to investigate the effect of food on the pharmacokinetic behavior of trihexyphenidyl. The trihexyphenidyl and internal standard trihexyphenidyl-d11 were extracted from human plasma by protein precipitation using methanol as the precipitant. Chromatographic separation was achieved on a Waters UPLC BEH C8 column (50 mm×2.1 mm, 1.7 μm) with 0.1% (v/v) formic acid aqueous solution containing 5 mmol/L ammonium acetate and acetonitrile-water (95:5, v/v) as the mobile phases. The analytes were detected by an electrospray ionization source in positive ion and multiple reaction monitoring modes. The linear range of trihexyphenidyl was 0.1-40 ng/mL. This test involved 30 healthy male and female subjects with a single oral administration of a 2-mg trihexyphenidyl hydrochloride tablet each. The 90% confidence intervals under fasting conditions of peak plasma concentration (Cmax), area under the plasma concentration-time curve (AUC0-t) and area under the plasma concentration-time curve from zero to infinity (AUC0-∞) were 82.2%-99.4%, 82.3%-97.3% and 83.4%-97.9%, and these pharmacokinetics parameters under postprandial conditions were 100.8%-122.8%, 96.8%-112.4% and 96.6%-112.1%, which were all in the range of 80.0%-125.0%, indicating that the test tablets and reference tablets were bioequivalent.

Key words: ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), human pharmacokinetics, bioequivalence, trihexyphenidyl

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