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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2014 Vol.15 No.11 P.929-939
Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study
Abstract: A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5–500, 5–500, 2.5–250, 1–100, 1–100, 1–100, and 1–100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%–9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies.
Key words: Ginkgo biloba tablet, Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), Pharmacokinetics
创新要点:运用超高压液相色谱-二级质谱连用法(UPLC-MS/MS)进行大鼠血浆中七种活性成分的测定,方法简单快速,适合于银杏叶制剂的药代动力研究。
研究方法:采用液液萃取进行血浆样品处理,该方法简单且快速。采用超高压液相色谱(UPLC)进行七种活性成分分离,达到了多种成分快速分离的目的。采用二级质谱(MS/MS)进行检测,优化质谱条件,减小了内源性干扰并提高检测灵敏度。经过专属性、线性、回收率、基质效应、精密度、准确度和稳定性考察,验证了该方法的适用性。经验证,该方法适用于银杏叶片的药代动力学研究。
重要结论:液液萃取处理血浆样品简单可靠,回收率稳定,无基质效应(表4)。UPLC-MS/MS能够快速、灵敏、专属性地分析大鼠血浆七种活性成分的血药浓度(表3和图3)。该方法适用于银杏叶片的七种活性成分的药代动力学研究(图4和5)。
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DOI:
10.1631/jzus.B1400035
CLC number:
R28
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On-line Access:
2024-08-27
Received:
2023-10-17
Revision Accepted:
2024-05-08
Crosschecked:
2014-10-15