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This chapter examines the early history of testing for abused drugs, starting in Vietnam, and traces its growth and expanded applications in the workplace, criminal justice, and schools. It also examines the role played by drug abuse-related accidents on the USS and Amtrak in shaping the field of drug testing. Standardization and process have been applied to this field of analysis through government regulation of mandated testing for government employees. The chapter examines the collection process, laboratory testing, review of test results, and the role of third-party administrators for workplace testing. These methods have also been applied to testing for the private sector. Standards for testing have also been influenced by a combination of technological advances that allow more accurate and useful test results, and government regulations that help ensure the reliability of the testing process.

A wide variety of body fluid specimens have been utilized for analysis for the presence of drugs of abuse. Urine has been and remains the most widely used body fluid specimen for routine testing for drugs of abuse, but several alternative specimens are establishing their place as suitable for drug testing. Hair, sweat, and oral fluid have reached a sufficient level of scientific credibility to be considered for use in the federally regulated workplace drug-testing programs. Each specimen provides different information about time and extent of use and likelihood of impairment. Some of these specimens (e.g., urine and oral fluid) can even be analyzed with simple on-site, noninstrumented testing devices, as well as through standard laboratory methods. These drugtesting tools, as objective pieces of information identifying drug use, have proven highly useful in addressing our society’s ongoing substance abuse challenges. This chapter reviews the use of these various body fluid specimens for drugs-of-abuse testing, addressing the balances between ease of specimen collection and handling, the ease and accuracy of analytical methods, the capability for sound interpretation of results, and, ultimately, legal defensibility.

Over the past few decades, a remarkable gamut of increasingly sophisticated technologies has been employed for the development of drug-testing applications. Recent advancements in analytical instrumentation and computer technologies have further expanded the capabilities and dimensions for drug testing and toxicological analysis. Technologies of different chemical principles can be used sequentially or in combination to accomplish the specific goals and requirements of the drug analysis programs. Ligand-binding assays such as immunoassays are commonly used for screening. Separation techniques such as chromatography or electrophoresis, as well as their coupling with powerful detectors such as mass spectrometry, can be effectively used for confirmatory testing of preliminary positive results or systematic analysis of generally unknown toxic compounds. Each of these technology categories can be further broken down into multiple selections for instrumentations and methodologies. This chapter presents a general overview of the commonly used analytical technologies and their utilities in drug testing. The analytical technologies afford a powerful means toward the detection, identification, and quantification of the presence of abused drugs in biological specimens. However, the overall interpretation of analytical results ought to take into consideration the reasons for testing and the performance characteristics of the applied technologies.

Microporous nitrocellulose membranes are used in lateral-flow assays as the substrate upon which immunocomplexes are formed and visualized to indicate the presence or absence of an analyte in a liquid sample. The pore sizes of membranes used in this application are comparatively large, ranging from 3 to 20 μm. Several attributes have resulted in nitrocellulose being the preferred substrate for lateral-flow assays. First, nitrocellulose adsorbs protein at a high level. Second, chemistries that make the membrane wettable with aqueous solution do not significantly diminish protein adsorption. Third, nitrocellulose membranes can be cast that have pores sufficiently large to allow lateral flow of fluid in a reasonable time. To facilitate the utilization of nitrocellulose in lateral-flow assays, the membrane can be cast directly onto a polyester backing. The backing does not interfere with the function of the nitrocellulose while significantly improving its handling properties. Optimal performance of nitrocellulose membranes requires an understanding of the interactions of test reagents with the nitrocellulose and the effects of reagent location on assay sensitivity.

In addition to the dry parts of a lateral-flow assay, there are also the biological components that allow the visualization of the results. Because of the relatively small size of a drug-of-abuse molecule, a competitive immunoassay with an antibody molecule conjugated to a colloidal gold particle is used. Antibodies can be polyclonal or monoclonal. In all cases, the antibodies have to be purified before use. Gold colloids are formed by the reduction of gold tetrachloric acid through a “nucleation” process. The size and shape of the colloids depend on the type and amount of reducer used. An accurate and reproducible lateral-flow assay requires the use of high-quality gold conjugates. The most common size of colloidal gold particle used is 40 nm. Conjugation of colloidal gold particles and antibodies depends on the availability and accessibility of three amino acid residues-lysine, tryptophan, and cysteine. Once a high-quality antibody-gold conjugate is formed, it can be applied to the conjugate pad either by soaking or by spraying. The drying process that follows is essential. It is affected by temperature, humidity, air flow, and pad thickness. Typically, forced-air systems are employed in conjunction with elevated temperature in the drying process. Finally, the proper functioning of a lateral-flow assay also depends on other nonbiological components, such as surfactants, blocking reagents, and buffers.

This chapter discusses materials selection, product design and tolerancing, and automated manufacturing processes to help in the efficient and cost-effective design and manufacture of lateral-flow assays. Raw materials including filter materials, membranes, and adhesives are discussed. A detailed discussion on properly dimensioning and tolerancing a typical lateral-flow laminate is provided. Several illustrations are provided to help in the understanding of proper dimensioning practices and to illustrate potentially problematic housing designs. The chapter concludes with six automation imperatives—six ideas that will help to ensure the successful and cost-effective implementation of automated manufacturing processes for the high-volume manufacturing environment.

Numerous devices are becoming available for collection and testing of oral fluids. The Intercept® device (Orasure Technologies), along with its associated immunoassays, is one of the first to be approved for commercial sale in the United States. This chapter presents clinical and nonclinical information on the principles of operation and performance of the Intercept device. This chapter specifically reviews the physiology of the oral cavity as it relates to the use of the Intercept device to collect specimens for analysis. Once a sample is prepared for analysis, performance data for numerous assays are reviewed. This includes analytical performance of various aspects of Intercept immuoassays used, including cross-reactivity, precision, limits of detection, and effects of interferents. Finally, clinical field data are included demonstrating the use of the Intercept device from large population prevalence studies.

The Dräger DrugTest® System (Dräger Safety) is a competitive, lateral-flow immunoassay for the detection of drugs of abuse in oral fluid. It is a point-of-care system comprised of an oral-fluid sample collector, test cassette, and analyzer, which delivers results read by the instrument for the simultaneous detection of the full National Institute on Drug Abuse (NIDA)-5 panel of drugs in a single oral-fluid sample. Oral-fluid testing has significant advantages over techniques involving blood or urine, such as its noninvasive nature, reduced costs and turnaround time, and reduced risk of sample adulteration; it also allows for accurate drug testing for a full NIDA-5 panel virtually anywhere and a more dignified treatment of test subjectsy. Dräger DrugTest is a product platform based on Up-Converting Phosphor Technology (UPT™ Orasure Technologies) and is used by law-enforcement agencies primarily to test operators and passengers of motor vehicles (i.e., roadside drug testing). This report provides an overview of the design of the system, the technology used, and the field studies in which the system has been tested.

Oral fluids have been generating increased interest as a matrix for abused drug testing. The present chapter describes an oral-fluid on-site detection device, Oratect®, which screens for six drugs simultaneously. Oratect integrates collection, testing, and confirmation sampling into a single device. The collection process is simple, and test results can be obtained within 5 to 6 min. The data collected so far suggest that it is a viable screening test. Recently, the testing has been extended to alcohol, so that a simultaneous determination of drugs and alcohol is possible.

Drugwipe® (Securetec Detektions-Systeme AG) is a pen-size detector for illegal drugs in saliva, in sweat, and on surfaces. It was first launched in 1995 to support drug law-enforcement police in their operations against smuggling and dealing of contraband. In 1996 the US Office for National Drug Control Policy (ONDCP) tested Drugwipe for its accuracy, sensitivity, and specificity in detecting invisible traces of narcotics on surfaces (). Since then, Drugwipe has been included in the technology transfer program of ONDCP.

With the increasing interest in saliva and sweat testing on the part of traffic police, the Drugwipe device has been significantly improved over the years. Today, Drugwipe is available for the detection of cocaine, opiates, cannabinoids, benzodiazepines, and amphetamines/methamphetamines (“ecstasy”). Drugwipe can be used to test oral fluids or sweat samples, or to detect invisible traces of narcotics. Commercially available Drugwipes include single, twin, and five-panel configurations. Drugwipe is especially designed for on-site applications and combines easy and rapid sampling with fast analysis. Drugwipe is used widely in Germany as a routine sweat or saliva test for roadside screening for driving under the influence of drugs (DUID). In the current Roadside Testing Assessment (ROSITA) II project, Drugwipe is under evaluation as a saliva test. The basic technology for analysis is lateral-flow immunoassay (see Chapters 3–6).

This chapter will first describe the technological basis of Drugwipe, including its major technical features. The second part will cover the various evaluation studies that have been performed using Drugwipe under controlled and general field conditions. Some of the data are not yet published.

Drugwipe can detect various benzodiazepines to as low as 5 ng/mL, and Δ9-tetrahydrocannabinol (THC) can be detected at 30 ng/mL. These sensitivities are currently unique for point-of-collection oral fluid/sweat test kits. The second part of this paper summarizes various published and unpublished data from trials and studies under controlled and general field conditions. Based on 1763 cases, a statistical evaluation by traffic police in Germany shows that more than 97% of all positive Drugwipe sweat tests are confirmed with positive blood results.