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超高效液相色谱-荧光检测法和基质辅助激光解析电离-离子淌度质谱法分析干血斑中阿米洛利和普萘洛尔的不均匀分布。

Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS.

机构信息

Analytical Chemistry Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Sarriena s/n, 48940 Leioa, Biscay, Basque Country, Spain.

出版信息

Molecules. 2019 Nov 26;24(23):4320. doi: 10.3390/molecules24234320.

DOI:10.3390/molecules24234320
PMID:31779239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6930677/
Abstract

Dried blood spot (DBS) has lately experienced an increase in its use in bioanalysis due to its several advantages compared with traditional blood sampling methods. Nevertheless, the use of DBS with quantitative purposes is hindered by the heterogeneous distribution of some compounds in the supporting matrix and the dependence of the response on different factors, such as the hematocrit, blood volume, and sampling position. In this study the effect of those factors in the analytical response was investigated by ultra high performance liquid chromatography coupled to fluorescence detection, using amiloride and propranolol as model compounds. The results showed a heterogeneous and drug-dependent distribution of the compounds in the blood spot. While amiloride concentration was higher in the center, propranolol concentration was higher in the periphery of the spot. Besides, the influence of the hematocrit on the quantitative results was observed. MALDI mass spectrometry imaging (MALDI-IMS) has allowed study of the distribution of the two cardiovascular drugs when they were placed in the DBS card using water:methanol solutions, demonstrating that they followed a similar distribution pattern as in blood. This work has showed the potentiality of the MALDI-IMS technique to predict the distribution of the drugs in the DBS card.

摘要

干血斑(DBS)由于与传统采血方法相比具有许多优势,最近在生物分析中得到了越来越多的应用。然而,由于某些化合物在支持基质中的不均匀分布以及响应对不同因素(如红细胞压积、血量和采样位置)的依赖性,DBS 用于定量目的受到阻碍。在这项研究中,使用阿米洛利和普萘洛尔作为模型化合物,通过超高效液相色谱法结合荧光检测法研究了这些因素对分析响应的影响。结果表明,化合物在血斑中的分布不均匀且具有药物依赖性。阿米洛利的浓度在中央较高,而普萘洛尔的浓度在斑点的外围较高。此外,还观察到红细胞压积对定量结果的影响。基质辅助激光解吸电离质谱成像(MALDI-IMS)允许使用水:甲醇溶液研究两种心血管药物在 DBS 卡上的分布,证明它们的分布模式与血液中的相似。这项工作表明 MALDI-IMS 技术有潜力预测药物在 DBS 卡中的分布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/a166f17dbacc/molecules-24-04320-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/51b5a8b0603e/molecules-24-04320-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/b7f2801cb487/molecules-24-04320-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/68f206e5f8d1/molecules-24-04320-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/a166f17dbacc/molecules-24-04320-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/51b5a8b0603e/molecules-24-04320-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/b7f2801cb487/molecules-24-04320-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/68f206e5f8d1/molecules-24-04320-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3444/6930677/a166f17dbacc/molecules-24-04320-g004.jpg

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本文引用的文献

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Is the hematocrit still an issue in quantitative dried blood spot analysis?在定量干血斑分析中,血细胞比容仍然是一个问题吗?
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Investigation of different approaches to incorporating internal standard in DBS quantitative bioanalytical workflows and their effect on nullifying hematocrit-based assay bias.探讨在干血斑定量生物分析工作流程中纳入内标的不同方法及其对消除基于血细胞比容的检测偏差的影响。
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A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS.一种使用液相色谱-串联质谱法对三环类抗抑郁药阿米替林、去甲替林、丙咪嗪、氯米帕明及其活性代谢物进行治疗药物监测的简单干血斑方法。
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Applying dried blood spot sampling with LCMS quantification in the clinical development phase of tasquinimod.在他喹莫德的临床开发阶段应用干血斑采样结合液相色谱-质谱联用定量分析。
Bioanalysis. 2015;7(2):179-91. doi: 10.4155/bio.14.259.
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The use of mass spectrometry to analyze dried blood spots.利用质谱分析法分析干血斑。
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Current strategies for coping with the hematocrit problem in dried blood spot analysis.干血斑分析中应对血细胞比容问题的当前策略。
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Simplifying sample pretreatment: application of dried blood spot (DBS) method to blood samples, including postmortem, for UHPLC-MS/MS analysis of drugs of abuse.简化样品预处理:将干血斑(DBS)方法应用于血液样本,包括死后样本,用于滥用药物的超高效液相色谱-串联质谱(UHPLC-MS/MS)分析。
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