Vol. 20 • Issue 7 • Page 84
Lab Limelight
According to a 2009 review in Bioanalysis, use of clinical urine drug tests (UDTs) to monitor patients prescribed controlled substances is a new aspect of clinical medicine that will play an increasing role as physicians treat chronic pain while trying to minimize abuse of opioid analgesics.1
UDT Advantages
Advantages of UDTs are their simplicity, low cost, noninvasive collection and sensitivity for drug detection as well as the breadth of laboratory knowledge on drug metabolite excretion and assay interpretation.1
Roger L. Bertholf, PhD, professor, Department of Pathology and Laboratory Medicine, and director, Clinical Chemistry, Toxicology and Point of Care Testing, University of Florida Health Science Center, Jacksonville, says, “Blood would give us a little more information about the amount of drug that had been taken because concentrations of drugs in blood are more reliably related to the dose than urinary concentrations, but blood is more difficult to collect. It’s more difficult to analyze than urine. And in most cases, the concentration is not the critical factor. It’s whether the drug is there at all.”
Limitations
Limitations of UDT include a slim window (hours to days) for detection and vulnerability to tampering.1 To mitigate these problems, authors (including Dr. Bertholf) in the 2009 review note that UDT may be complemented by other testing methods such as hair, oral fluid and, less commonly, sweat.
Another obstacle is that most physicians are not proficient interpreting UDT results. Proper interpretation requires knowledge of all prescription, over-the-counter and herbal drugs and nutritional supplements that can influence results as well as drug metabolism, metabolite interconversions and detection method characteristics, which may necessitate communication between physicians and lab professionals.
“What we found through several surveys conducted of physicians who use urine drug testing in their practices was they are unfamiliar with a number of very important aspects of how those drugs are measured and the limitations of the methods,” Dr. Bertholf says. “Whereas it may seem straightforward to order a screen for opiates, for example, methods used to detect opiates don’t detect all drugs in that class. Among the ones they do detect, they don’t detect them equally. So if you’re not aware of those limitations or how sensitive the method is for various opiates, you may misinterpret the results.”
FDA-approved Tests
Most FDA-approved UDT immunoassay tests utilize homogeneous immunoassay approaches. The tests, all of which are automated, include fluorescence polarization, an enzyme multiplied immunoassay technique, a cloned enzyme donor immunoassay and kinetic interaction of microparticles in solution. All but fluorescence polarization can be adapted to various clinical analyzers, Dr. Bertholf says.
Confirmatory Testing
Urine screens using immunoassays utilize antibodies produced in a manufacturing process that aren’t 100% specific. Additionally, some drug compounds appear chemically similar because of the pharmaceutical development process. As a result, authors of the 2009 review say unexpected results should be subjected to confirmatory tests and consultative support from a lab director, toxicologist or certified medical review officer. Gas chromatography mass spectrometry (GC/MS) can also serve as backup testing.
“For example, when we do a screen for opiates, it will detect both morphine and codeine because they are chemically similar compounds,” Dr. Bertholf says. “But the result of the immuno-assay doesn’t tell you which one is there. Mass spectrometry is able to identify a specific drug.”
Furthermore, authors say a predicted increase in legal challenges to unfavorable results of UDT may prompt a shift toward handling of specimens in a forensically defensible way. In a forensic setting, the identity of every specimen is questioned, Dr. Bertholf explains.
“They must have some kind of documentation that the specimen is actually from the person whose name is on the container or the paperwork that accompanies the specimen, and that documentation would include the signature of anyone who had handled that specimen between the time it was collected and the time it arrives in the laboratory,” he says, referring to the chain of custody.
Though he isn’t sure if this level of verification/documentation is practical for the clinical lab, Dr. Bertholf says it may be important when someone being tested will suffer a penalty based on results of a drug screen.
Jill Hoffman is managing editor.
References
1. Reisfield GM, Goldberger BA, Bertholf RL. False-positive and false-negative test results in clinical urine drug testing. Bioanalysis 2009;1(5)1-16.
2. Reisfield GM, Goldberger BA, Crews BO, Pesce AJ, Wilson GR,Teitelbaum SA and Bertholf RL. Ethyl Glucuronide, Ethyl Sulfate, and Ethanol in Urine after Sustained Exposure to an Ethanol-Based Hand Sanitizer. J Anal Toxicol 2011;35;85-90.
Related Products
Biosite Inc., an Inverness Medical company
Triage® Drugs of Abuse Panels from Biosite Inc., an Inverness Medical company, offer rapid, highly accurate screens for up to nine classes of abused drugs. Two (one positive, one negative) built-in reactive controls are cost effective, while amphetamines/methamphetamines assays share one detection zone. A visual signal indicates positive, and the panels require no calibration, moving parts or maintenance. Hospitals can obtain consistently accurate results in minutes, so physicians have information to decide on the most effective treatment.
Randox Laboratories
RX series systems from Randox Laboratories can be used as dedicated analyzers for urine drug of abuse (DoA) screening in labs where demands for drug screening are increasing. The Ximola™ is a compact, fully automated random-access benchtop analyzer offering 400 photometric tests and 240 ISE tests per hour. The system offers Windows-based software, user-defined QC capacity, low water usage, multi-speed stirring, low service requirements, reusable Pyrex® cuvettes and multilevel password access.
Siemens Healthcare Diagnostics
The latest FDA-approved Siemens Healthcare Diagnostics drug-of-abuse test, the Emit® II Plus 6-Acetylmorphine Assay, enables fast, selective testing for heroin use. Urine presence of 6-Acetylmorphine (6-AM), a heroin metabolite, confirms heroin use; the new assay tests for this metabolite and is intended for qualitative/semi-quantitative determination of 6-AM at a 10 ng/mL cutoff concentration. Providing high specificity without cross-reactivity to morphine, morphine metabolites and many common analgesics, the assay also delivers low analytical sensitivity (down to 1.1 ng/mL) and greater than 99% agreement with the reference method (GC/MS).
