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一种经过验证的用于定量大鼠血浆中杰尔文并研究其在大鼠体内药代动力学的新型超高效液相色谱-串联质谱法。

A New UPLC-MS/MS Method Validated for Quantification of Jervine in Rat Plasma and the Study of Its Pharmacokinetics in Rats.

作者信息

Chen Lianguo, Weng Qinghua, Ma Jianshe

机构信息

Wenzhou People's Hospital, Wenzhou 325000, China.

School of Basic Medicine, Wenzhou Medical University, Wenzhou 325035, China.

出版信息

J Anal Methods Chem. 2019 Mar 7;2019:5163625. doi: 10.1155/2019/5163625. eCollection 2019.

Abstract

The aim of this study was to develop an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess the concentration of jervine in rat plasma and its pharmacokinetics. Diazepam was used as internal standard (IS). The chromatographic separation of jervine and IS was carried out on an UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 m) with a flow rate of 0.4 mL/min. A mixture of acetonitrile and water (0.1% formic acid) was used as a mobile phase. The UPLC-MS/MS was equipped with an electrospray ionization (ESI), adopting multiple reactive monitoring mode to determine jervine in rat plasma. The retention times of jervine and the internal standard were 1.71 and 2.13 min, respectively. The calibration curve of jervine ranged between 1 and 1000 ng/mL. The lower limit of quantitation (LLOQ) was 1 ng/mL, and the lower limit of determination (LLOD) was 0.2 ng/mL. The accuracy was ±6%; the interday precision and intraday precision were no more than 9%. The recovery was higher than 90.3%, and the matrix effect was lower than 10%. The UPLC-MS/MS method was successfully developed and used for the application of the pharmacokinetic study. The primary pharmacokinetic parameters of jervine in this study were as follows: the AUC was 969.3 ± 277.7 ng/mL·h, the was 506.6 ± 192.8 ng/mL, the CL/F was 1.7 ± 0.5 L/h/kg, and the was 3.4 ± 1.2 h.

摘要

本研究的目的是建立一种超高效液相色谱-串联质谱法(UPLC-MS/MS),以测定大鼠血浆中浙贝乙素的浓度及其药代动力学。地西泮用作内标(IS)。浙贝乙素和内标的色谱分离在UPLC BEH C18柱(2.1 mm × 50 mm,1.7 μm)上进行,流速为0.4 mL/min。乙腈和水(0.1%甲酸)的混合物用作流动相。UPLC-MS/MS配备电喷雾电离(ESI),采用多反应监测模式测定大鼠血浆中的浙贝乙素。浙贝乙素和内标的保留时间分别为1.71和2.13 min。浙贝乙素的校准曲线范围为1至1000 ng/mL。定量下限(LLOQ)为1 ng/mL,测定下限(LLOD)为0.2 ng/mL。准确度为±6%;日间精密度和日内精密度均不超过9%。回收率高于90.3%,基质效应低于10%。成功建立了UPLC-MS/MS方法并用于药代动力学研究。本研究中浙贝乙素的主要药代动力学参数如下:AUC为969.3 ± 277.7 ng/mL·h,Cmax为506.6 ± 192.8 ng/mL,CL/F为1.7 ± 0.5 L/h/kg,tmax为3.4 ± 1.2 h。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b016/6431447/09e7edfa473b/JAMC2019-5163625.001.jpg

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