About 200 million people use illicit drugs each year globally, according to a 2007 report released by the United Nations. In the United States, the Drug Abuse Warning Network reported that more than 54% of drug-related hospital visits involved multiple drugs.

With drug abuse on the rise, there has been a concomitant increase in testing for such abuse by a variety of organizations. A number of manufacturers currently produce devices for testing in response to the increased demand. A new generation of automated testing devices offers even more speed, efficiency, and accuracy in drugs of abuse (DOA) testing.

In a clinical setting, drug screens are ordered to identify, rule in, or rule out the presence of drugs. Urine is usually used for DOA testing because it's the most convenient sample to obtain and it gives the most complete picture.

Scott Ramey, vice president of clinical drugs of abuse marketing for Biosite Inc, San Diego, an Inverness Medical company, says although many types of lateral-flow DOA testing devices are used for such purposes as job screening, testing in prisons, and other purposes, his company also manufactures testing devices specifically designed for clinical labs.

Triage Drugs of Abuse Panel

The first of two types of Triage® drug screens, the Triage Drugs of Abuse Panel, was developed in 1992 and is still in use today by more than 900 US hospitals. "It's unique because unlike other testing devices, including our own, the appearance of a colored line indicates a positive result; in other words, that the drug being tested for is present at a level greater than the assay threshold. All other visual rapid drug screens use the appearance of a line or of color to indicate a negative result," Ramey says.

The Triage DOA Panel is performed with three steps. A urine sample is transferred to a well, incubates, then is transferred to the membrane where three drops of a wash solution is applied. The entire procedure takes about 10 minutes, Ramey says, compared to about 5 minutes for most lateral flow tests. He said the Triage product is also slightly costlier than others but is easy to use.

The test is generally performed in hospital labs. CLIA categorizes the complexity of performing the test as "moderate," Ramey says.

Drug screening in US hospitals is performed predominantly by lab analyzers or rapid kits. Analyzers and rapid kits are used for such testing as employee screening and generally look for the presence of amphetamine, methamphetamine, cocaine, opiates, PCP, and THC.

Biosite's Triage Meter

Triage TOX Drug Screen

Hospitals also assay for barbiturates, benzodiazepines, methadone, and tricyclic antidepressants, as well as propoxyphene, and some companies have specific tests to detect low levels of oxycodone. Ramey says that Biosite's Triage TOX Drug Screen (which provides results in about 15 minutes) also includes a test for acetaminophen within the panel.

Symptoms of an acetaminophen overdose may take many hours to exhibit. However, an overdose may potentially damage a person's liver unless an antidote is given within 4 to 8 hours of ingestion.

Nearly 500 people per year die from such overdoses, Ramey notes. So although 70% to 90% of quantitative acetaminophen tests are negative, hospitals still order them. "Because acetaminophen is so common in so many things, various guidelines suggest including it in urine screens," he says.

The emergency department (ED) orders drug screens for several reasons. Drug-screen results are needed prior to admitting patients to a psych ward, Ramey says. Labor and delivery cases may also require DOA screens if no prenatal history is available. Nonclinical hospital uses include employee testing, occupational health, and pain management.

Patients presenting to the ED with chest pain may also require a drug screen. Cocaine-induced chest pain is of concern because beta blockers may be used for treatment; however, beta blockers are contraindicated in patients who have used cocaine.

With the Triage TOX Drug Screen, a urine sample is delivered into a cartridge that is then inserted into a meter that reads the device's reaction and displays either a positive or negative result. The Triage meter can print the result out and download it automatically. The unit is about the size of a telephone and can report results for 11 tests in about 15 minutes. Many labs have converted to this system from visual products, Ramey says, because it reduces human transcription and interpretation errors.

Nanogen's ToxSTATus™

ToxSTATus Kit

Nanogen's ToxSTATus™ product is used mostly in clinical areas such as hospitals. It's useful for any organization that needs a quick and easy test that's also inexpensive. Testing is done for those DOA on which the marketplace focuses. The device can test for five to 10 drugs on a panel, including amphetamines, cocaine, and THC. The kits are storable since they do not require refrigeration, says Nelson Batista, Canadian territory manager and support, Nanogen Point-of-Care Diagnostics Division, Toronto.

Testing is done on urine. Results are obtained in about 3 to 5 minutes and can be read when a control line turns red. Batista says the correlation rate is more than 99%, compared to large centralized automated testing systems, but that correlation varies depending on the drug for which the test is ordered.

He says the ToxSTATus device resembles a pregnancy test and uses the same technology but looks for different molecules. Pregnancy tests look for a specific hormone; with DOA tests, the search is for a specific drug analyte in the sample.

The ToxSTATus device consists of a plastic housing with a membrane in the middle and a sample pad at one end. That's where the reagents are contained. The urine sample is picked up in the sample pad, and as it passes through the membrane, lines appear indicating whether drugs are not present.

If a red line appears, that indicates a negative result. If no line appears, the result is positive. The ToxSTATus test is very simple to read and contains instructions right on the device, showing what positive or negative results look like.

What's in the future? "Delivery systems may change, but in terms of technology, immuno-specificity is the ultimate testing method," Batista says. "The interaction between antigens and antibodies won't change. These are critical components and won't be replaced."

DOA testing does reveal other things, Batista says, such as the presence of prescription drugs. Many drugs are legitimately used, and in these cases technologists should run confirmatory tests, but that doesn't always happen because most of what's detected are prescription drugs.

"People do take amphetamines and codeine for legitimate reasons," he says—in cough medicines, for example. The test will detect those drugs, so a follow-up would be necessary. Another example: A person being tested who shows positive for methadone might be in a rehabilitation program and taking the drug legitimately.

Batista notes that the ToxSTATus device is also used for the prevention of drug reactions. Such testing is mandatory in some states on patients who come into hospital EDs unconscious or otherwise unable to tell physicians what medications they're taking. It is vital for physicians and nurses to know if these patients need to be managed differently.

Batista says drug abuse is on the rise. One of the biggest increases is in the use of methamphetamines, which is included on the ToxSTATus panels. That's according to the California Department of Alcohol and Drug Program's California Government Meth Treatment Guide 2007.

TOX/See POC Device

The current DOA test-ing product from Bio-Rad Laboratories, Hercules, Calif, is TOX/See™. Jason Lai, PhD, Bio-Rad senior product manager, says Bio-Rad is also developing a new toxicology assay on a fully automated multiplexing system that tests urine for the presence of such commonly abused substances as amphetamines, methamphetamines, opiates, methadone, cocaine, phencyclidine, THC, benzodiazepines, barbiturates, tricyclic antidepressants, and MDMA (Ecstasy).

TOX/See is a one-step, handheld POC device for the qualitative detection of 14 drugs or drug metabolites in human urine based on lateral flow chromatographic immunoassay testing. It requires no instrument to operate and no reagent to process the urine sample. Each test device is individually packed in a pouch, making it easy to carry to the testing site near the patient.

It is easy to use with a minimal training, and provides results in 5 minutes. The TOX/See product portfolio covers the commonly abused substances and also includes specific tests for emerging DOA, such as buprenorphine, MDMA, oxycodone, and propoxyphene.

Most of Bio-Rad's TOX/See testing is performed in hospitals. The process works as follows: When a patient comes in, their urine is collected in a cup. A TOX/See foil pouch is opened. Inside are a testing device and a small dropper to dispense the urine sample. Three drops of urine are placed into each well, where it mixes with components and antibody particles.

The urine interacts with antibodies in the well and conjugates in the testing region, a competitive binding process. Drugs in the urine compete with the antibody to the binding sites of the test strip. If the urine does not contain any of the drugs for which the test is ordered, the antibody particles bind the conjugates at each testing site on the test strip and cause a colored line to appear.

When the concentration of a particular drug is below the test's cutoff level, the color line still appears indicating below the cutoff level. When it exceeds the cutoff, no color line is indicated because the drug saturates all biding sites, preventing antibody particles from attaching to the conjugate. A control line indicates whether the test is valid. If urine migration does not occur, the test will fail and the control line will not be visible. The result interpretation is simple to read and is also printed on the testing cassette device.

Several types of drugs can be simultaneously tested, but most of those used are 10-drug testing panels. Results can be obtained in about 5 minutes. The accuracy rate is from 93% to 99% in agreement with GC/MS among 14 analytes.

BIOPlex 2200 Toxicology Panel

Bio-Rad's new fully automated BioPlex® 2200 System, with autoimmune disease and infectious disease testing panels, uses magnetic beads, and its multiplex technology allows for simultaneous testing of up to 22 markers in a single patient sample. The BioPlex 2200 toxicology panel will test for 11 drug classes and/or metabolites from a small sample of urine and can process 100 patient samples per hour, enabling a test throughput of up to 1,100 test results per hour. It enables random access and stat sample processing with up to 8 hours of walkaway operation, allowing workflow flexibility, fast turnaround time, and laboratory savings, particularly for high-volume DOA testing laboratories.

Gary Tufel is a contributing writer for CLP.