在一项初步临床研究中，对受试者采集的人干血斑样本中对乙酰氨基酚及其葡萄糖醛酸苷和硫酸酯代谢物进行同步液相色谱-串联质谱定量分析。

Simultaneous LC-MS/MS quantitation of acetaminophen and its glucuronide and sulfate metabolites in human dried blood spot samples collected by subjects in a pilot clinical study.

作者信息

Li Wenkui, Doherty John P, Kulmatycki Kenneth, Smith Harold T, Tse Francis Ls

机构信息

Department of Drug Metabolism & Pharmacokinetics, Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, NJ 07936, USA.

出版信息

Bioanalysis. 2012 Jun;4(12):1429-43. doi: 10.4155/bio.12.119.

DOI:10.4155/bio.12.119

PMID:22793028

Abstract

BACKGROUND

In support of a pilot clinical trial using acetaminophen as the model compound to assess dried blood spot (DBS) sampling as the method for clinical pharmacokinetic sample collection, a novel sensitive LC-MS/MS method was developed and validated for the simultaneous determination of acetaminophen and its major metabolites, acetaminophen glucuronide and sulfate, in human DBS samples collected by subjects via fingerprick.

RESULTS

The validated assay dynamic range was from 50.0 to 5000 ng/ml for each compound using a 1/8´´ (3-mm) disc punched from a DBS sample. Baseline separation of the three analytes was achieved to eliminate the possible impact of insource fragmentation of the conjugated metabolites on the analysis of the parent. The overall extraction efficiency was from 61.3 to 78.8% for the three analytes by direct extraction using methanol.

CONCLUSION

The validated method was successfully implemented in the pilot clinical study with the obtained pharmacokinetic parameters in agreement with the values reported in literature.

摘要

背景

为支持一项以对乙酰氨基酚作为模型化合物的临床试验，该试验旨在评估将干血斑（DBS）采样作为临床药代动力学样本采集方法的可行性，开发并验证了一种新型灵敏的液相色谱-串联质谱（LC-MS/MS）方法，用于同时测定受试者通过手指针刺采集的人DBS样本中的对乙酰氨基酚及其主要代谢物对乙酰氨基酚葡萄糖醛酸苷和硫酸酯。