Liang Xiaorong, Yang Lulu, Berezhkovskiy Leonid, Liederer Bianca, Nguyen Trung, Jia Wei, Schweiger Michelle, Dean Brian, Deng Yuzhong
Drug Metabolism & Pharmacokinetics, Genentech Inc., South San Francisco, CA 94080, USA.
Bioanalysis. 2011 Oct;3(20):2291-302. doi: 10.4155/bio.11.205.
Dried blood spot (DBS) sampling has received growing interest mainly in regulatory preclinical and clinical studies while not routinely used in exploratory discovery pharmacokinetic screening. An intravenous bolus cassette dose of six compounds in rats followed by hemolyzed blood sample (HBS) and DBS sampling was evaluated in this study.
A sensitive liquid chromatography tandem mass spectrometry method was developed and qualified for the simultaneous determination of six compounds in rat whole blood using DBS or HBS techniques. The concentrations obtained from DBS samples matched well with those from HBS for each individual compound.
This study demonstrated the applicability of DBS sampling for cassette dosing in discovery pharmacokinetics screening.
干血斑(DBS)采样主要在监管的临床前和临床研究中受到越来越多的关注,而在探索性发现药代动力学筛选中未常规使用。本研究评估了在大鼠中静脉注射一次包含六种化合物的弹丸式给药方案,随后进行溶血血样(HBS)和DBS采样。
开发了一种灵敏的液相色谱串联质谱法,并验证其可使用DBS或HBS技术同时测定大鼠全血中的六种化合物。对于每种化合物,从DBS样品获得的浓度与从HBS获得的浓度匹配良好。
本研究证明了DBS采样在发现药代动力学筛选中弹丸式给药的适用性。