Schumacher Sarah, Seitz Harald
Fraunhofer Institute for Cell Therapy and Immunology, Bioanalytics und Bioprocesses, Am Mühlenberg 13, 14476 Potsdam, Germany; Humboldt University Berlin, Department of Biology, Invalidenstr. 110, 10115 Berlin, Germany.
Fraunhofer Institute for Cell Therapy and Immunology, Bioanalytics und Bioprocesses, Am Mühlenberg 13, 14476 Potsdam, Germany.
J Immunol Methods. 2016 Sep;436:34-40. doi: 10.1016/j.jim.2016.06.004. Epub 2016 Jun 23.
An immunoassay was established which enables a reliable quantification of serological drug samples. The assay is based on a competitive ELISA. In total nine drugs (amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol (THC), phencyclidine (PCP), methadone, morphine, cocaine and benzoylecgonine) were tested. All reagents had to pass through a stringent validation process. Within the established test for three out of the nine drugs no cross-reactivity with any tested compounds, e.g. serum, other antibodies or chemically related molecules was detectable for the tested antibodies. Furthermore, a sensitive and selective detection was possible, even in the presence of up to 9 drugs or of various anti-drug antibodies. After exclusion of cross-reactivities antibodies against three drugs (methadone, MDMA, benzoylecgonine) were validated, which allowed a specific and sensitive quantification. For the competitive measurements CVs in the range of 2-17% could be reached with LLOQs of 10ng/mL and LODs of 150ng/mL for methadone, 250ng/mL for MDMA and 400ng/mL for benzoylecgonine. Anonymized serum samples (n=10) provided by the office of criminal investigation Berlin were analyzed for verification purposes. Evaluation of these data showed a correlation (CV) of ≈0.9 with standard GC-MS methods. A miniaturization on microarray was possible by using the anti-MDMA antibody for the detection of MDMA in serum. The microarray increased the through-put drastically and enabled the simultaneous quantification of various drugs.
建立了一种免疫测定法,可对血清学药物样本进行可靠定量。该测定法基于竞争性酶联免疫吸附测定(ELISA)。总共测试了九种药物(苯丙胺、甲基苯丙胺、3,4-亚甲基二氧基甲基苯丙胺(摇头丸)、四氢大麻酚(THC)、苯环己哌啶(PCP)、美沙酮、吗啡、可卡因和苯甲酰爱康宁)。所有试剂都必须经过严格的验证过程。在针对九种药物中的三种所建立的测试中,对于测试抗体,未检测到与任何测试化合物(如血清、其他抗体或化学相关分子)的交叉反应。此外,即使存在多达九种药物或各种抗药物抗体,也能够进行灵敏且选择性的检测。在排除交叉反应后,针对三种药物(美沙酮、摇头丸、苯甲酰爱康宁)的抗体得到了验证,这使得能够进行特异性和灵敏的定量。对于竞争性测量,美沙酮的最低定量限(LLOQ)为10ng/mL,检测限(LOD)为150ng/mL;摇头丸的LLOQ为250ng/mL;苯甲酰爱康宁的LLOQ为400ng/mL,变异系数(CV)范围为2 - 17%。为进行验证分析了由柏林刑事调查办公室提供的匿名血清样本(n = 10)。对这些数据的评估显示与标准气相色谱 - 质谱(GC - MS)方法的相关性(CV)约为0.9。通过使用抗摇头丸抗体检测血清中的摇头丸,可实现微阵列的小型化。微阵列极大地提高了通量,并能够同时对多种药物进行定量。