Assessment of paper spray ionization for quantitation of pharmaceuticals in blood spots
Assessment of paper spray ionization for quantitation of pharmaceuticals in blood spots
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DOI：
10.1016/j.ijms.2010.06.037
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发表时间：
2011-03-01
影响因子：
1.8
通讯作者：
Cooks, R. Graham
中科院分区：
文献类型：
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作者：
Manicke, Nicholas E.;Yang, Qian;Cooks, R. Graham
纸喷雾使用溶剂电喷雾，通过向湿基底施加高电压，从沉积在纸或其他多孔介质上的样品产生气相离子。该方法适用于小分子和大分子的分析，并在此应用于来自干血斑的药物，使其可能用于临床试验期间的药物定量或用于医院或诊所的治疗药物监测。探讨了与纸喷雾分析干血斑中药物的分析特性有关的几个问题。（1）通过比较普萘洛尔（PRN）和阿替洛尔（ATN）（两种具有广泛不同的蛋白质结合特性的药物）在水和血液中的比例，以及通过将PRN的氘代类似物掺入已经含有PRN的血液中，然后使血液孵育不同长度的时间，来研究蛋白质-药物相互作用的影响。在第一个实验中，PRN与ATN的比例在水和血液中是相同的。在第二个实验中，PRN和PRN d 7的比率是相同的，不管允许氘代类似物在血液中平衡多久。这些结果表明，蛋白质结合不影响分析物信号，因此至少在这种情况下，纸喷雾测量血液中的总药物浓度。(2)对掺入同位素标记的内标物（IS）的替代方法进行了测试，这是分析干血斑中药物时获得定量结果所需的。因为在采集点将标准品加入到液体血液中通常是不可行的，所以必须以某种方式将IS掺入干燥的血液中。将IS PRN d 7与含有PRN的干燥血斑以三种不同的方式组合：通过用IS溶液预处理纸，通过将IS掺杂到喷雾溶剂中，以及通过将IS溶液添加到DBS的冲压部分。当在添加血液之前将IS添加到纸上或之后将其添加到干血打孔中时，该方法的方差小于8%。当将IS加入溶剂洗脱液中时，方差为16%。在所有情况下，PRN的恢复低于IS。(3)最后，通过测量从纯溶液到空白血液到含有1 μ g/mL PRN的血液的基质中PRN d 7获得的信号来评估基质效应。发现纯溶液给出比血液高约10倍的信号，表明正在发生电离抑制。高浓度PRN的存在不影响PRN d 7的响应。(C)2010 Elsevier B. V.保留所有权利。
Paper spray uses solvent electrospray to produce gas phase ions from samples deposited on paper or other porous media by applying a high voltage to the wet substrate. The method is amenable to the analysis of small and large molecules and is applied here to pharmaceuticals from dried blood spots, making it potentially useful for quantitation of drugs during clinical trials or for therapeutic drug monitoring in a hospital or clinic. Several topics related to the analytical characteristics of paper spray for analyzing drugs in dried blood spots are explored. (1)The effect of protein-drug interactions was studied by comparing the ratio of propranolol (PRN) and atenolol (ATN), two drugs with widely disparate protein binding properties, in water and in blood and by spiking a deuterated analog of PRN into blood already containing PRN and then allowing the blood to incubate for different lengths of time. In the first experiment, the ratio of PRN to ATN was the same in both water and blood. In the second experiment, the ratio of PRN and PRN d7 was the same regardless of how long the deuterated analog was allowed to equilibrate in the blood. These results suggest that protein binding does not affect analyte signal, and that paper spray therefore measures the total drug concentration in blood at least in this case. (2) Alternative methods for incorporation of the isotopically labeled internal standard (IS), which is needed for quantitative results when analyzing drugs in dried blood spots, were tested. Because it is often not feasible to add the standard to the liquid blood at the point of collection, the IS must be incorporated into the dried blood in some way. The IS PRN d7 was combined with dried blood spots containing PRN in three different ways: by pretreating the paper with an IS solution, by doping the IS into the spray solvent, and by adding an IS solution to a punched out section of a DBS. The variance of the method was less than 8% when the IS was added to the paper either before adding the blood or when adding it afterwards to the dried blood punch. The variance was 16% when the IS was added to the solvent eluent. In all cases, the recovery of PRN was lower than that of the IS. (3) Finally, matrix effects were assessed by measuring the signal obtained for PRN d7 in matrices ranging from neat solution, to blank blood, to blood containing 1 mu g/mL of PRN. A neat solution was found to give approximately 10 times higher signal than blood, indicating that suppression of ionization is occurring. The presence of a high concentration of PRN did not affect the response for PRN d7. (C) 2010 Elsevier B.V. All rights reserved.