Stability of benzodiazepines and cocaine in blood spots stored on filter paper
Stability of benzodiazepines and cocaine in blood spots stored on filter paper
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DOI：
10.1093/jat/32.7.511
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发表时间：
2008-09-01
影响因子：
2.5
通讯作者：
Anderson, Robert A.
中科院分区：
文献类型：
--
作者：
Alfazil, Abdulkareem A.;Anderson, Robert A.
先前的研究表明，血液中的药物浓度在储存过程中会发生变化，尤其是在室温下，但即使是不稳定的药物，如可卡因，在干燥的血斑（DBS）中也可能保持稳定。建立了一种分析滤纸上血斑中水解不稳定药物的新方法，以评估其在一个月的储存期间的降解情况。所选药物包括氟硝西泮、替马西泮、恶西泮、劳拉西泮、硝西泮、地西泮和可卡因。将100µL含有浓度为1000 ng/mL的药物的血液涂在Guthrie卡片903上，在室温下放置过夜晾干。滤纸在萃取缓冲液中悬浮1h，超声作用。然后使用Clean Screen®柱固相萃取从缓冲液中提取药物，并通过液相色谱-串联质谱分析。方法验证结果表明，在5 ~ 200 ng/点的浓度范围内，各标准曲线均呈良好的线性关系，相关系数为0.994 ~ 0.999。3种浓度（10、50和100 ng/点）的日间和日间精密度分别为1.6-18.3%和2.8-14.7%。检测限为0.29 ~ 0.74 ng/点，定量下限为0.99 ~ 2.46 ng/点。加样回收率在81 ~ 106%之间。DBS一式两份，分别在室温、4°C和- 20°C下保存一个月。DBS中药物在所有储存条件下的降解率均低于同等条件下相应的液体血液样品，每种分析物均可从样品中回收80%以上。
Previous studies have shown that drug concentrations in blood can change during storage, especially at room temperature, but even labile drugs such as cocaine may be stable in dried blood spots (DBS). A new method has been developed for the analysis of hydrolytically labile drugs in blood spots on filter paper in order to assess their degradation during a storage period of one month. The drugs selected included flunitrazepam, temazepam, oxazepam, lorazepam, nitrazepam, diazepam, and cocaine. A Guthrie card 903 was spotted with 100 µL of blood containing the drugs at concentrations of 1000 ng/mL and left overnight to dry at room temperature. The filter paper was suspended in extraction buffer for 1 h with ultrasonication. Drugs were then extracted from the buffer by solid-phase extraction using Clean Screen®columns and analyzed by liquid chromatography-tandem mass spectrometry. Method validation showed that all calibration curves were linear over the concentration range 5–200 ng/spot with correlation coefficients of 0.994–0.999. Interday and intraday precisions at three concentrations (10, 50, and 100 ng/spot) were 1.6–18.3% and 2.8–14.7%, respectively. Limits of detection were 0.29–0.74 ng/spot, and lower limits of quantitation were 0.99–2.46 ng/spot. Recoveries of all analytes were in the range 81–106%. DBS were stored in duplicate at room temperature, 4°C, and −20°C for up to one month. Degradation of the drugs in DBS at all storage conditions was less than for the corresponding liquid blood samples stored under similar conditions and more than 80% of each analyte could be recovered from the samples.