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Analyst. 2010 Apr;135(4):720-5. doi: 10.1039/b922329k.
A novel approach to the quantitative determination of xenobiotics in whole blood samples without sample preparation or chromatography is described. This method is based on direct analysis of microlitre volumes of blood which are spotted onto specialized paper cards and dried, with the resulting dried blood spots (DBS) analyzed directly via desorption electrospray ionization (DESI) mass spectrometry (MS). Using sitamaquine, terfenadine, and prazosin as model compounds with verapamil as a common internal standard, this methodology demonstrated detection of each compound down to 10 ng mL(-1) from DBS where standard calibration curves show linearity from 10-10,000 ng mL(-1) with r(2) > 0.99. Three (3) different untreated types of filter papers (Whatman 903 and 31ETF as well as Ahlstrom 237) and two (2) treated types of filter paper (Whatman FTA and FTA Elute) were examined and the effect of each surface on the recovery of each analyte was evaluated. The results show that the untreated papers provide the best substrates for DBS analysis by DESI. A more in depth study of the quantitation of sitamaquine on 31ETF paper stock provided bias and error measurements of less than 20%. The promising results shown in this study may have important implications in the areas of therapeutic drug monitoring (TDM), clinical and forensic toxicology, and pharmacology.
本文描述了一种无需样品制备或色谱分离即可直接分析全血样品中新型外来化合物的定量方法。该方法基于直接分析微升体积的血液,将血液点样到专用的纸片上并干燥,然后通过解吸电喷雾电离(DESI)质谱(MS)直接分析得到的干血斑(DBS)。以疟喹、特非那定和普萘洛尔作为模型化合物,维拉帕米作为常见的内标,该方法证明了从 DBS 中检测到每种化合物的浓度低至 10ng/mL,标准校准曲线的线性范围为 10-10000ng/mL,r(2)>0.99。研究了三种(3)种未经处理的滤纸(Whatman 903 和 31ETF 以及 Ahlstrom 237)和两种(2)种经过处理的滤纸(Whatman FTA 和 FTA Elute),评估了每种表面对每种分析物回收率的影响。结果表明,未经处理的纸张是通过 DESI 进行 DBS 分析的最佳基质。对 31ETF 纸基上疟喹定量的更深入研究提供了小于 20%的偏倚和误差测量值。本研究中显示的有希望的结果可能对治疗药物监测(TDM)、临床和法医毒理学以及药理学领域具有重要意义。