An analytical strategy to characterize the pharmacokinetics and pharmacodynamics of triptorelin in rats based on simultaneous LC–MS/MS analysis of triptorelin and endogenous testosterone in rat plasma

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• 作者：Jiangbin Han (1) (2)
  Shu Zhang (3)
  Wanhui Liu (2) (3)
  Guangyi Leng (2)
  Kaoxiang Sun (2)
  Youxin Li (2)
  Xin Di (1)
  
• 关键词：Triptorelin ; Testosterone ; LC–MS/MS ; Pharmacokinetics/pharmacodynamics ; Plasma
• 刊名：Analytical and Bioanalytical Chemistry
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：406
• 期：9-10
• 页码：2457-2465
• 全文大小：831 KB
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• 作者单位：Jiangbin Han (1) (2)
  Shu Zhang (3)
  Wanhui Liu (2) (3)
  Guangyi Leng (2)
  Kaoxiang Sun (2)
  Youxin Li (2)
  Xin Di (1)
  
  1. Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China
  2. State Key Laboratory of Long-acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co. Ltd, Yantai, 264003, China
  3. School of Pharmacy, Yantai University, Yantai, 264005, China
  
• ISSN：1618-2650

文摘

Triptorelin, a gonadotropin-releasing hormone agonist, has been used in the treatment of hormone-responsive prostate cancer by inducing testosterone suppression. Research on the relationship between the time courses of triptorelin and testosterone is very important, but accurate quantification of triptorelin and testosterone simultaneously in biological specimens is a challenging analytical problem. In the present study, a rapid, sensitive, and selective method for simultaneous determination of triptorelin and testosterone in rat plasma by solid-phase extraction and liquid chromatography–tandem mass spectrometry was developed using a ZORBAX RRHD Eclipse Plus C8 column (2.1?×-0?mm, 1.8?μm) with a 0.05?% propionic acid/methanol gradient. In view of the polarity difference between the two analytes, two internal standards, i.e., leuprolide and testosterone-13C3, were used for individual quantitation of triptorelin and testosterone. Endogenous testosterone was determined by reference to a calibration curve prepared using testosterone-D3 as a surrogate analyte. The method exhibits excellent linearity over three orders of magnitude for each analyte. The lower limit of quantification was 0.01?ng/mL for triptorelin and 0.05?ng/mL for testosterone, with consumption of 100?μL of plasma. The method was successfully applied to characterize the pharmacokinetics and pharmacodynamics of slow-release 28-day form triptorelin acetate biodegradable microspheres in rats after intramuscular injections of three consecutive doses of 0.6?mg/kg per 28?days. The results revealed that the pharmacokinetic profile of triptorelin produced an initial flare-up in testosterone levels, rapid castration within 5?days after injection, and long-term castration until the next dose. Figure Analytical strategy to characterize the PK/PD properties of triptorelin