PDF(Pubmed)
Abstract：
Toxicology testing is performed in clinical settings, forensic settings, and for controlling doping. Drug screening is a toxicology test to determine if drugs are present in biological samples. The most common specimen type for drug testing is urine, as drugs and/or their metabolites are often more concentrated in the urine, extending the detection window of drugs. The dilute-and-shoot method is a simple procedure used in toxicology testing, where a sample is diluted before being directly injected into the liquid chromatography-mass spectrometry (LC-MS) system. This method is easy, quick, and cost-saving, and can be used for protein-poor liquid specimens such as urine. Thus, it is reasonable and attractive for busy toxicology laboratories to combine the dilute-and-shoot method with high-resolution hyphenated-MS for urine drug screening. This method has several disadvantages, including a suboptimal detection capability for certain analytes, as well as interference from co-eluting matrix components called matrix effects, in which co-eluting matrix molecules alter the ionization efficiency of the analyte molecules at the ionization source in LC-MS, altering (mostly reducing) the analyte detection capability. The matrix effect testing is essential for the validation of LC-MS-based assays. A reasonable approach to addressing these undesirable effects would be to minimize these components. The most straightforward approach is to reduce the amounts of matrix components by using a higher dilution of the specimen and a lower volume for specimen injection. Optimization of the chromatographic separation is another reasonable approach for reducing co-eluting matrix components with the analyte.
摘要：
毒理学测试在临床环境中进行，法医设置,和控制掺杂。药物筛选是一种毒理学测试，用于确定药物是否存在于生物样品中。药物检测最常见的样本类型是尿液，因为药物和/或其代谢物通常在尿液中更集中，扩大药物的检测窗口。稀释和射击方法是一种用于毒理学测试的简单程序，其中样品在直接注入液相色谱-质谱(LC-MS)系统之前被稀释。这个方法很简单,快,节约成本,可用于尿液等蛋白质贫乏的液体标本。因此，对于繁忙的毒理学实验室来说，将稀释和射击方法与高分辨率连字符MS相结合用于尿液药物筛选是合理且有吸引力的。这种方法有几个缺点，包括对某些分析物的次优检测能力，以及来自称为基体效应的共洗脱基质成分的干扰，其中共洗脱基质分子改变LC-MS中电离源处分析物分子的电离效率，改变(主要降低)分析物检测能力。基质效应测试对于基于LC-MS的测定的验证是必不可少的。解决这些不期望的影响的合理方法是使这些组分最小化。最直接的方法是通过使用较高的样本稀释度和较低的样本注射体积来减少基质组分的量。色谱分离的优化是减少与分析物共洗脱的基质组分的另一种合理方法。
