Kacinko Sherri L, Barnes Allan J, Kim Insook, Moolchan Eric T, Wilson Lisa, Cooper Gail A, Reid Claire, Baldwin Dene, Hand Chris W, Huestis Marilyn A
Chemistry and Drug Metabolism Section, Intramural Research Program, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Forensic Sci Int. 2004 Apr 20;141(1):41-8. doi: 10.1016/j.forsciint.2003.12.003.
Oral fluid is an interesting alternative matrix for drug testing in many environments, including law enforcement, workplace drug testing, and drug treatment facilities. Performance characteristics of the FDA-cleared, qualitative, Cozart RapiScan Opiate Oral Fluid Drug Testing System (Opiate Cozart RapiScan System or Opiate CRS) were compared to the semi-quantitative Cozart Microplate EIA Opiate Oral Fluid Kit (Opiate ELISA) and to gas chromatography/mass spectrometry (GC/MS). The following oral fluid opiate cutoffs were evaluated: the GC/MS limit of quantification (LOQ) of 2.5 mg/l; 15 microg/l currently used for oral fluid testing in the United Kingdom (UK); 30 microg/l (Opiate CRS cutoff); and 40 microg/l, the proposed Substance Abuse and Mental Health Services Administration (SAMHSA) cutoff. Subjects provided informed consent to participate in this IRB-approved research and resided on the closed research ward throughout the study. Three oral codeine doses of 60 mg/70 kg were administered over a 7-day period. After a 3-week break, subjects received three doses of 120 mg/70 kg within 7 days. Oral fluid specimens (N = 1273) were analyzed for codeine (COD), norcodeine (NCOD), morphine (MOR) and normorphine (NMOR) by GC/MS with an LOQ of 2.5 microg/l for all analytes. MOR and NMOR were not detected in any sample; 26.5% of the specimens were positive for COD and 13.7% for NCOD. Opiate CRS uses a preset, qualitative cutoff of 10 microg/l; this is equivalent to 30 microg/l in undiluted oral fluid as the oral fluid collection process involves a 1:3 dilution with buffer. Sensitivity, specificity, and efficiency of Opiate CRS compared to Opiate ELISA were 98.6, 98.1, and 98.2% at a 30 microg/l cutoff and 99.0, 96.2, and 96.6% at a 40 microg/l cutoff. Compared to the much lower GC/MS LOQ of 2.5 microg/l, sensitivity, specificity and efficiency were 66.8, 99.3 and 90.7%. Increasing the GC/MS cutoff to the current UK level yielded performance characteristics of 81.5% (sensitivity), 99.3% (specificity), and 95.4% (efficiency). Using a GC/MS cutoff identical to the preset Opiate CRS cutoff yielded sensitivity, specificity, and efficiency of 88.5, 99.2, and 97.5%, respectively. At the proposed SAMSHA confirmation cutoff of 40 microg/l, sensitivity increased with little change in specificity and efficiency (91.3% sensitivity, 98.9% specificity, and 97.5% efficiency). Oral fluid is a suitable matrix for detecting drugs of abuse. Opiate CRS, with a 30 microg/l cutoff, is sufficiently sensitive, specific and efficient for oral fluid opiate analysis, performing similarly to Opiate ELISA at the same cutoff, and having performance characteristics >91% when compared to GC/MS at the proposed SAMHSA cutoff.
在包括执法、工作场所药物检测和戒毒治疗机构等许多环境中，口腔液是一种用于药物检测的有趣替代基质。将美国食品药品监督管理局（FDA）批准的定性Cozart RapiScan阿片类口腔液药物检测系统（阿片类Cozart RapiScan系统或阿片类CRS）的性能特征与半定量的Cozart微孔板酶免疫分析阿片类口腔液试剂盒（阿片类酶联免疫吸附测定）以及气相色谱/质谱联用（GC/MS）进行了比较。对以下口腔液阿片类药物临界值进行了评估：GC/MS的定量下限（LOQ）为2.5毫克/升；英国目前用于口腔液检测的15微克/升；30微克/升（阿片类CRS临界值）；以及物质滥用和精神健康服务管理局（SAMHSA）提议的40微克/升临界值。受试者提供了知情同意书以参与这项经机构审查委员会（IRB）批准的研究，并在整个研究过程中居住在封闭的研究病房。在7天内给予三剂60毫克/70千克的口服可待因。经过3周的休息后，受试者在7天内接受三剂120毫克/70千克的药物。通过GC/MS对口腔液样本（N = 1273）进行可待因（COD）、去甲可待因（NCOD）、吗啡（MOR）和去甲吗啡（NMOR）分析，所有分析物的LOQ为2.5微克/升。在任何样本中均未检测到MOR和NMOR；26.5%的样本COD呈阳性，13.7%的样本NCOD呈阳性。阿片类CRS使用预设的10微克/升定性临界值；这相当于未稀释口腔液中的30微克/升，因为口腔液采集过程涉及与缓冲液1:3稀释。与阿片类酶联免疫吸附测定相比，阿片类CRS在30微克/升临界值时的灵敏度、特异性和效率分别为98.6%、98.1%和98.2%，在40微克/升临界值时分别为99.0%、96.2%和96.6%。与低得多的GC/MS LOQ 2.5微克/升相比，灵敏度、特异性和效率分别为66.8%、99.3%和90.7%。将GC/MS临界值提高到英国当前水平，得到的性能特征为81.5%（灵敏度）、99.3%（特异性）和95.4%（效率）。使用与预设阿片类CRS临界值相同的GC/MS临界值，灵敏度、特异性和效率分别为88.5%、99.2%和97.5%。在提议的SAMHSA确认临界值40微克/升时，灵敏度增加，特异性和效率变化不大（灵敏度91.3%、特异性98.9%、效率97.5%）。口腔液是检测滥用药物的合适基质。阿片类CRS的临界值为30微克/升，对于口腔液阿片类药物分析具有足够的灵敏度、特异性和效率，在相同临界值下与阿片类酶联免疫吸附测定表现相似，与提议的SAMHSA临界值下的GC/MS相比，性能特征>91%。
