New & Improved!

Evolving Chemistry Automation Supports Drugs of Abuse Testing
May 2018 - Vol. 7 No. 4 - Page #20

Since the earliest use of automated chemistry systems for testing multiple analytes from a patient sample in the 1950s, advances in qualitative testing for drugs of abuse (DOA) have resulted in a largely hands-off approach using today’s multifaceted technology. Throughout these advancements, the precision and accuracy of testing has increased, ensuring the results laboratory scientists produce are expedient and appropriate.

Testing for the burgeoning array of drugs and other abused substances is growing in need, thus DOA testing is an area of clinical practice significantly affected by the expanded types and capabilities of clinical chemistry testing automation. In the last decade alone, the emergence and proliferation of so-called designer drugs (eg, “Spice” and other synthetic cannabinoids), has placed pressure on the clinical laboratory to keep pace and provide clinicians detailed identification and quantification. Fortunately, improvements in drug testing scope and methodology, including oral fluid point-of-care testing devices and additional screening methods, have allowed the lab to remain abreast of DOA issues, and the related ongoing education has produced laboratorians with a wide range of toxicology training.

Early Days of Testing for Drugs of Abuse

Prior to Leonard Skeggs’ introduction of the first practical and completely automated chemistry testing system for urea, glucose, and calcium—the AutoAnalyzer—laboratories utilized manual quantitative analysis measurements of chemical change via individual assessments using methods such as gasometry, potentiometry and amperometry, flame emission photometry, spectrophotometry, and electrophoresis.3 Initial automated chemistry instruments offered a limited range of chemical analyses, which did not include drugs of abuse. Wide ranging DOA testing did not become routinely incorporated into laboratory workflow until these analytes came under increased scrutiny by employment and law officials in the 1980s.4

Norman G. Anderson helped introduce centrifugal analysis to clinical laboratory instrumentation in the late 1960s.3 These instruments incorporated multiple testing methodologies within a single device enabling laboratory professionals to reduce the amount of patient sample needed to accomplish the same mission. With the introduction of specially designed assay reagent kits, test menus for automated chemistry instruments grew to include drugs of abuse.

Initially, DOA testing was done in the form of a qualitative, positive/negative test. Health care providers and employers were generally interested only in the presence (or lack thereof) of a small number of specific substances in a patient sample, not the concentration. Thus, DOA testing was distilled to a simple paper strip that changes color when it comes into contact with certain drugs. However, as the number and type of intoxicating substances ingested by humans continues to grow and diversify, enhancements in chemistry automation have led to a proliferation of automated tests performed on a single sample.

More recent improvements to chemistry analyzers have seen the addition of fully automated, highly-specialized analytical methods such as solid phase extraction liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS).5 The technology behind this sophisticated methodology was originally developed for research purposes, but was later incorporated into clinical DOA and other chemical analytes testing. Many clinical laboratories have now implemented this capability for special chemistry testing, as well as some electrophoresis testing. LC/MS instrumentation is highly sensitive and selective in DOA testing, and while the initial investigative analytes were for marijuana and cocaine, test menus have expanded in response to the increasing number of drugs currently in use.

Current Trends with Drugs of Abuse

The growth of recreational drug use has expanded the need for enhanced testing and treatment modalities. A drug of abuse that has grown common in recent years is Spice, the synthetic cannabinoid associated closely to marijuana. This compound originated overseas but has seen strong growth within the US drug population having been sold in herbal and health-food stores as a “natural product” to the tune of over $5 billion a year.6 To date, multiple versions of Spice have been introduced to the open market that include delta-9 tetrahydrocannabinol, the primary psychoactive component of cannabis.5

One of the most difficult aspects of identifying and measuring Spice intoxication is that due to its synthetic nature, the composition of the drug is constantly changing. This requires laboratories to perform a battery of tests that could detect cannabinoids or similar compounds measureable in a urine or blood sample, including but not limited to JWH-018 metabolites, 5-fluoro ADB (and metabolites), PB-22 hydroxyquinolines, and additional metabolites. To adjust for this kind of chemical evolution and as these and other recreational drugs become more sophisticated, qualification and quantification testing must evolve as well.

New DOA Technologies

Enabling dynamic testing, the matrix sample for drug testing has expanded from the original urine analysis to employ commercially available drug testing kits that measure breath, hair, and tissue samples, in addition to urine, sweat, blood, and oral fluid. The latter option can be performed using immunoassay for rapid qualitative and presumptive detection of DOA.7 This is an example of a handheld qualitative test capable of producing results from a buccal cheek swab. Screening in this manner has a reported sensitivity of 91% for DOA.1

Among the most recent technologies developed for DOA testing include a smartphone application and light box reader that enables a laboratory technician to perform highly accurate pH measurements on a test strip using a colorimetric detection system together with a calibration technique to compensate for measurement errors due to ambient light variablility.7 This system was developed to measure DOA in both oral fluid or sweat excretions and is capable of testing samples with a cutoff level as low as 5 ng/mL for some DOA. These kinds of portable applications promise to provide high resolution image sensors, wireless connectivity, and processing capabilities that capture, store, and transmit data. Confirmatory testing would still require routine samples to be sent to an external central or reference laboratory. However, as computational power has expanded while its components have reduced in size, basic clinical chemistry laboratory testing is now available in the palm of your hand.


Clinical detection of DOA has expanded over time due largely to continued growth in the range of abused substances. With several states legalizing medical and, in some cases, recreational marijuana, the management of DOA testing must remain both flexible and accurate for both medical providers and the clients and communities they serve. Through the utilization of modern chemistry analyzers along with miniaturized and novel testing modalities, DOA testing can be achieved quickly, accurately, and inexpensively.


  1. Allen KR. Screening for Drugs of Abuse: Which Matrix, Oral Fluid or Urine? Ann Clin Biochem. 2011;48(Pt 6):531-541.
  2. Wolters Kluwer. Employment Law Daily website newsletter. SHRM poll reveals half of employers conduct drug tests on final job candidates. Accessed 3/30/2018.
  3. Armbruster DA, Overcash DR, Reyes J. Clinical Chemistry Laboratory Automation in the 21st Century- Amat Victoria curam (Victory loves careful preparation). Clin Biochem Rev. 2014;35(3):143-153.
  4. Russell J. Industry News: History of Workplace Drug Testing in the US. Confirm Biosciences. September 6, 2016. Accessed 3/22/2018.
  5. Yao B, Lian L, Pang W, et al. Determination of Illicit Drugs in Aqueous Environmental Samples by Online Solid-Phase Extraction Coupled to Liquid Chromatography-Tandem Mass Spectrometry. Chemosphere. 2016;160:208-215.
  6. Spaderna M, Addy PH, D’Souza DC. Spicing Things Up: Synthetic Cannabinoids. Psychopharmacology. 2013;228(4):525-540.
  7. Carrio A, Sampedro C, Sanchez-Lopez JL, et al. Automated Low-Cost Smartphone-Based Lateral Flow Saliva Test Reader for Drugs-of-Abuse Detection. Sensors. 2015;15(11):29569-29593.

Lt Col Paul Eden, MT(ASCP), MBA, PhD, United States Air Force (retired), is an adjunct professor of pharmacology & toxicology at Wright State University in Dayton, Ohio. Previously, he served as chief of laboratory services in the 88th Diagnostics & Therapeutics Squadron, 88th Medical Group, 88th Air Base Wing, Wright Patterson air force base in Ohio. He received his BS in cell biology at the University of California, Davis, and his PhD in environmental toxicology from Mississippi State University.

Need for DOA Testing

Drug testing has expanded well beyond its traditional focus on addiction treatment. While toxicology testing in drug abuse clinics remains substantial, workplace testing (pre-employment screening and ongoing employment testing) continues to be highly prevalent in the US and is gaining interest in some European countries. Drug testing is now routinely performed at hospitals and general practice/surgical centers, and within sports organizations and the criminal justice system, to name a few.1

In the US, 57% of employers require drug testing for all job candidates, and just 29% do not conduct such testing on any candidates. That said, drug testing existing employees is far less common with just 36% of organizations performing post-employment testing.2

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