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采用液相色谱-串联质谱法测定大鼠血浆中紫檀芪 a 的含量及其药代动力学研究。

Quantification of thonningianin a in rat plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.

机构信息

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, PR China.

Department of Pharmacy, Jinan Maternity and Child Care Hospital, Jinan, PR China.

出版信息

Pharm Biol. 2021 Dec;59(1):525-531. doi: 10.1080/13880209.2021.1913188.

Abstract

CONTEXT

Thonningianin A is an ellagitannin substance and displays multiple pharmacological activities.

OBJECTIVE

This study investigated the pharmacokinetic characteristics of thonningianin A after oral administration in rats using a fully validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.

MATERIALS AND METHODS

A sensitive and selective LC-MS/MS assay was developed for quantifying thonningianin A. Eighteen Wistar rats were randomly divided into three groups ( = 6), which were given at a single dose of 10, 20, or 40 mg/kg thonningianin A by gavage. Blood samples (200 µL) were collected from the orbit vein at designated time points and analyzed using the LC-MS/MS method to measure the levels of thonningianin A.

RESULTS

Thonningianin A and internal standard (IS) were eluted at 1.5 and ∼3.0 min, respectively. The selected reaction mode transitions monitored were 873.2 > 300.3 and 819.3 > 610.6 for thonningianin A and the IS, respectively. The calibration range was 10-1200 ng/mL. The intra- and the inter-day accuracy and precision met the acceptance criteria. No carryover and matrix effect were observed. The plasma concentrations of thonningianin A increased rapidly after oral administration of three dosages and reached the mean peak concentrations () within 0.61-0.83 h. Meanwhile, AUC/AUC of the three dosage groups was more than 89.0% (10 mg/kg), 95.7% (20 mg/kg), and 97.0% (40 mg/kg).

DISCUSSION AND CONCLUSIONS

The present method is the first report in terms of the simple precipitation procedure, high sensitivity, and high-throughput efficiency. This validated assay was successfully applied to determine the pharmacokinetic behaviours of thonningianin A in rats. This study should be helpful for providing references for understanding the action mechanism and further application of .

摘要

背景

Thonningianin A 是一种鞣花单宁物质,具有多种药理活性。

目的

本研究采用完全验证的液相色谱-串联质谱(LC-MS/MS)法研究 Thonningianin A 灌胃给药后的药代动力学特征。

材料和方法

建立了一种灵敏、选择性的 LC-MS/MS 测定方法用于定量 Thonningianin A。18 只 Wistar 大鼠随机分为三组(每组 6 只),分别灌胃给予 10、20 或 40mg/kg Thonningianin A。在指定时间点从眶静脉采集 200µL 血样,采用 LC-MS/MS 法测定 Thonningianin A 的浓度。

结果

Thonningianin A 和内标(IS)分别在 1.5 和 ∼3.0min 洗脱。监测的选择反应模式转换为 Thonningianin A 和 IS 的 873.2 > 300.3 和 819.3 > 610.6。校准范围为 10-1200ng/mL。日内和日间精密度和准确度均符合要求。未观察到拖尾和基质效应。三种剂量给药后,Thonningianin A 的血浆浓度迅速升高,在 0.61-0.83h 内达到平均峰浓度()。同时,三个剂量组的 AUC/AUC 均大于 89.0%(10mg/kg)、95.7%(20mg/kg)和 97.0%(40mg/kg)。

讨论与结论

本方法是首次报道采用简单沉淀法、高灵敏度和高通量效率。该验证后的方法成功应用于测定大鼠体内 Thonningianin A 的药代动力学行为。本研究有助于为了解其作用机制和进一步应用提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d7/8871622/98c971d18b8b/IPHB_A_1913188_F0001_B.jpg

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