Li Wenkui, Doherty John P, Kulmatycki Kenneth, Smith Harold T, Tse Francis Ls
Department of Drug Metabolism & Pharmacokinetics, Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, NJ 07936, USA.
Bioanalysis. 2012 Jun;4(12):1429-43. doi: 10.4155/bio.12.119.
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.
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.
The validated method was successfully implemented in the pilot clinical study with the obtained pharmacokinetic parameters in agreement with the values reported in literature.
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。
使用从DBS样本上冲下的1/8英寸（3毫米）圆片，每种化合物的验证分析动态范围为50.0至5000 ng/ml。实现了三种分析物的基线分离，以消除共轭代谢物的源内碎裂对母体分析的可能影响。通过甲醇直接萃取，三种分析物的总体萃取效率为61.3%至78.8%。
验证后的方法在试点临床研究中成功实施，获得的药代动力学参数与文献报道的值一致。
