BACKGROUND Dried specimens have been proposed in multiple environments to minimize costs associated with specimen storage and shipping in clinical studies. This report describes the development and validation of an automated method for qualitative toxicology screening of dried urine samples using LC-MS/MS. METHODS Urine standards containing 41 compounds were prepared and applied to filter paper cards. Dried urine was eluted from the cards using a Dried Blood Spot (DBS) autosampler from Spark Holland, which was plumbed inline with a Thermo Scientific Turboflow chromatography system for subsequent MS/MS detection with selected reaction monitoring. Limits of detection, precision of peak areas, repeatability, and carryover studies were conducted. Concordance with a reference LC-MS/MS method using liquid samples was evaluated using remnant discarded specimens. RESULTS The limit of detection ranged from 5 to 75 ng/mL for most compounds. At the LOD for each analyte, the peak area precision ranged from 8 to 29%. For 20 repeat injections of samples spiked at ±25% of the LOD, there was a 4% false positive rate for the 75% × LOD samples, and a 0.4% false negative rate for the +125% × LOD samples. In comparing 40 known positive specimens analyzed with the DUS method and a liquid urine reference method, there was 88% agreement. Analysis of 10 known negative specimens yielded negative results. There was no significant carryover detected up to 2000 ng/mL for any of the analytes in the assay. CONCLUSION Using a robotic DUS sampling an inline HTLC-MS/MS system, we have developed and validated a fully-automated and robust method for multi-analyte detection of drugs of abuse in dried urine specimens.

中文翻译：

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自动分析干尿斑（DUS）样品以进行毒理学筛查。

背景技术已经提出了在多种环境中干燥样品以最小化与临床研究中的样品存储和运输相关的成本。本报告描述了使用LC-MS / MS对干燥尿液样品进行定性毒理学筛查的自动化方法的开发和验证。方法制备了包含41种化合物的尿液标准品，并将其应用于滤纸卡。使用来自Spark Holland的干血斑（DBS）自动进样器从证卡上洗脱干尿，将其与Thermo Scientific Turboflow色谱系统在线对接，以进行随后的MS / MS检测并选择反应监测功能。进行了检测限，峰面积的精密度，可重复性和残留研究。使用残留的标本评估与使用液体样品的参考LC-MS / MS方法的一致性。结果对于大多数化合物，检测限范围为5至75 ng / mL。在每种分析物的LOD处，峰面积精度为8％至29％。对于重复进样达到LOD±25％的样品20次，75％×LOD样品的假阳性率为4％，+ 125％×LOD样品的假阴性率为0.4％。在比较用DUS方法和液体尿液参考方法分析的40个已知阳性样本时，有88％的一致性。对10个已知阴性样本的分析得出阴性结果。分析中的任何分析物均未检测到高达2000 ng / mL的显着残留。结论使用机器人DUS对在线HTLC-MS / MS系统进行采样，