科研之友
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摘要
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.
- 出版日期2011-3-1
