干血样生物分析的优化

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Journal of pharmacological and toxicological methods Pub Date : 2023-09-01 DOI:10.1016/j.vascn.2023.107296
Elham Ataei Alizadeh , Georg Rast , Chris Cantow , Jessica Schiwon , Florian Krause , Guido R.Y. De Meyer , Pieter-Jan Guns , Brian D. Guth , Michael Markert
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引用次数: 0

摘要

药物动力学/药效学建模已成为了解药物开发中药物暴露和反应关系的一种有价值的技术。药代动力学数据通常是通过采集多个血液样本获得的,这可能会干扰生理参数并使研究设计复杂化。可佩戴的自动血液采样系统可以通过在不干扰心血管参数的情况下在可编程的时间点收集干燥的血液样本来改善这一限制。本研究的目的是与传统的血液取样技术相比,评估DBS的生物分析,并优化在滤纸带上干燥的犬血中掺入的各种化合物的回收率。方法将比格犬培养后的血样中加入16种不同的化合物,并将全血样品的一半离心以获得血浆。将干燥的血样滴干燥后,使用液相色谱-质谱法对样品进行分析。该研究探索了不同的抗凝剂、样品制备方法和技术方法,以最佳地测定干血样品中的化合物浓度。结果通过对两种抗凝剂的测试,并采用我们所采用的优化的样品制备方法和技术方法,干血样品的生物分析可以提供与传统采血技术相当的结果。讨论自动化血液取样系统有可能提供更多的血液样本,在不干扰生理参数的情况下,在安全药理学研究中提供更多的药代动力学数据。它们可以为各种其他类型的研究或分析提供一种可行的替代传统的获取血液的方法。
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Optimization of bioanalysis of dried blood samples

Introduction

Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape.

Methods

Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples.

Results

With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques.

Discussion

Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.

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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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