O'Neal C L, Crouch D J, Rollins D E, Fatah A A
Center for Human Toxicology, University of Utah, Department of Pharmacology and Toxicology, Salt Lake City 84112, USA.
J Anal Toxicol. 2000 Oct;24(7):536-42. doi: 10.1093/jat/24.7.536.
The use of a variety of alternative biological specimens such as oral fluid for the detection and quantitation of drugs has recently been the focus of considerable scientific research and evaluation. A disadvantage of drug testing using alternative specimens is the lack of scientific literature describing the collection and analyses of these specimens and the limited literature about the pharmacokinetics and disposition of drugs in the specimen. Common methods of oral fluid collection are spitting, draining, suction, and collection on various types of absorbent swabs. The effect(s) of collection techniques on the resultant oral fluid drug concentration has not been thoroughly evaluated. Reported is a controlled clinical study (using codeine) that was designed to determine the effects of five collection techniques and devices on oral fluid codeine concentrations. The collection techniques were control (spitting), acidic stimulation, nonacidic stimulation, and use of either the Salivette or the Finger Collector (containing Accu-Sorb) oral fluid collection devices. Preliminary data were collected from two subjects using the Orasure device. The in vitro drug recovery was also evaluated for the Salivette and the Finger Collector devices. With the exception of a single time point, codeine concentrations in specimens collected by the control method (spitting) were consistently higher than concentrations in specimens collected by the other methods. The control collection concentrations averaged 3.6 times higher than concentrations in specimens collected by acidic stimulation and 1.3 to 2.0 higher than concentrations in specimens collected by nonacidic stimulation or collection using either the Salivette or the Finger Collector devices. When calculated using oral fluid codeine concentrations from the clinical study, the elimination rate constant, t(1/2), AUC and the peak oral fluid concentrations demonstrated device differences. The slope of the elimination curve for codeine using the acidic collection method exceeded that of the other four methods. As a result, the t(1/2) for the acidic method was significantly less than that of the control method (1.8 vs. 3.0 h, respectively). Oral contamination contributed to the control method having higher AUC than that calculated using the other methods. There was considerable variation in peak codeine concentrations between devices and between individuals within each collection method. When samples were collected simultaneously with the Salivette and the Finger Collector, the mean codeine concentrations were similar. We were able to recover > or = 500 microL of oral fluid from 81.8% of the clinical samples collected with the Salivette. However, we were able to recover this volume from only 25.5% of the samples collected with the Finger Collector. In addition, the in vitro drug recoveries were lower using the Finger Collector. When oral fluid was collected nearly simultaneously by the control method and by use of the Salivette, mean control codeine concentrations were 2.3 times higher, but the duration of detection was similar for both methods.
使用多种替代生物样本(如口腔液)进行药物检测和定量,最近已成为大量科学研究和评估的焦点。使用替代样本进行药物检测的一个缺点是,缺乏描述这些样本采集和分析的科学文献,以及关于药物在样本中的药代动力学和处置的有限文献。常见的口腔液采集方法有吐唾、引流、抽吸以及在各种类型的吸收性拭子上采集。采集技术对所得口腔液药物浓度的影响尚未得到充分评估。本文报道了一项对照临床研究(使用可待因),该研究旨在确定五种采集技术和装置对口腔液可待因浓度的影响。采集技术包括对照(吐唾)、酸性刺激、非酸性刺激以及使用唾液采集器或手指采集器(含Accu - Sorb)口腔液采集装置。使用奥瑞捷装置从两名受试者收集了初步数据。还对唾液采集器和手指采集器装置的体外药物回收率进行了评估。除了单个时间点外,通过对照方法(吐唾)采集的样本中的可待因浓度始终高于通过其他方法采集的样本中的浓度。对照采集浓度平均比酸性刺激采集的样本中的浓度高3.6倍,比非酸性刺激或使用唾液采集器或手指采集器装置采集的样本中的浓度高1.3至2.0倍。根据临床研究中的口腔液可待因浓度计算,消除速率常数、t(1/2)、AUC和口腔液峰值浓度显示出装置差异。使用酸性采集方法时可待因消除曲线的斜率超过其他四种方法。因此,酸性方法的t(1/2)明显小于对照方法(分别为1.8小时和3.0小时)。口腔污染导致对照方法的AUC高于使用其他方法计算的AUC。在各采集方法中,不同装置之间以及个体之间可待因峰值浓度存在相当大的差异。当同时使用唾液采集器和手指采集器采集样本时,可待因平均浓度相似。使用唾液采集器采集的临床样本中,我们能够从81.8%的样本中回收≥500微升的口腔液。然而,使用手指采集器采集的样本中只有25.5%能够回收此体积的口腔液。此外,使用手指采集器时体外药物回收率较低。当通过对照方法和使用唾液采集器几乎同时采集口腔液时,对照可待因平均浓度高2.3倍,但两种方法的检测持续时间相似。