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采用液相色谱-串联质谱法对人深部脑刺激(DBS)样本进行美托洛尔及其代谢物O-去甲基美托洛尔的对映体选择性测定。

Human DBS sampling with LC-MS/MS for enantioselective determination of metoprolol and its metabolite O-desmethyl metoprolol.

作者信息

Liang Xiaorong, Jiang Hongliang, Chen Xi

机构信息

Department of Bioanalytical Chemistry, Covance Laboratories Inc. 3301 Kinsman Blvd, Madison, WI 53704, USA.

出版信息

Bioanalysis. 2010 Aug;2(8):1437-48. doi: 10.4155/bio.10.107.

Abstract

BACKGROUND

The dried blood spots (DBS) sampling technique has been gaining wide interest in preclinical and clinical studies due to its inherent advantages. However, the impact of DBS sampling on chiral compounds in terms of stability and detection sensitivity has not been studied yet.

RESULTS

A high-throughput, sensitive and enantioselective LC-MS/MS-based bioanalytical method was developed and validated for the simultaneous determination of individual enantiomers of metoprolol and its metabolite O-desmethylmetoprolol (O-DMM)in human whole blood using the DBS sampling technique.

CONCLUSIONS

The developed DBS LC-MS/MS assay has a run time of 3 min, shorter than all previous methods while achieving complete baseline separation of enantiomeric metoprolol and O-DMM. This study demonstrates the applicability of DBS for chiral molecules analysis.

摘要

背景

干血斑(DBS)采样技术因其固有优势在临床前和临床研究中受到广泛关注。然而,DBS采样对手性化合物的稳定性和检测灵敏度的影响尚未得到研究。

结果

开发并验证了一种基于液相色谱-串联质谱(LC-MS/MS)的高通量、灵敏且对映体选择性的生物分析方法,用于使用DBS采样技术同时测定人全血中美托洛尔及其代谢物O-去甲基美托洛尔(O-DMM)的各对映体。

结论

所开发的DBS LC-MS/MS测定法运行时间为3分钟,比以往所有方法都短,同时实现了美托洛尔对映体和O-DMM的完全基线分离。本研究证明了DBS在手性分子分析中的适用性。

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