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At AIT, we pride ourselves on developing tests that satisfy the needs of our clients. But what happens when clients have different needs for the same test? R&D Project Manager Coleen Carroll, Ph.D. sheds light on the process.
AIT’s first priority is to ensure that a test provides value to our clients. If it’s not clinically useful to healthcare practitioners (HCPs) monitoring patient compliance or helpful to a coroner determining cause of death, we won’t create the test. Literature research and client feedback help us make this determination. AIT is constantly receiving feedback from HCPs and coroners on what their needs and challenges are. We take this feedback seriously and respond by providing tests that meet those needs.
There are two stages to creating a new test – method development and validation. Method development typically involves extensive literature research and experiments to establish sample preparation, instrument parameters and the detection range. Development can take anywhere from two weeks to a couple of months or more depending on how much is known about the drug; the less that is known, typically the more trial-and-error that occurs.
Once the conditions are set, the R&D chemist validates the method using industry standard protocols in which strict criteria have to be met. Validation entails that accuracy, precision, linearity, selectivity, ion suppression, matrix effects and exogenous interferences have been assessed and meet industry standards necessary for a quality method. Patient specimens that test positive for the analyte of interest or spiked specimens are used in the development and validation process. Sometimes during validation, criteria aren’t met for a specific test (e.g., ion suppression) and the R&D chemist returns to development to resolve the issue. Once the issue is resolved – however long that takes – validation can commence again.
Matrix is a key factor in determining how a method will be developed. For blood, we have to research the properties of the analyte/drug such as the blood elimination half-life to help determine what the cut-off level should be. For urine, we research how the analyte/drug is metabolized, since we will likely need to monitor at least one metabolite to verify ingestion.
It depends on the service line. A urine test is more effective for an HCP monitoring patient compliance to prescribed medications, but the need for blood analysis in compliance is growing as more HCPs realize urine results can’t be used to estimate the amount of drug the patient is actually taking.
For coroners, a blood test is extremely valuable since the amount of drug in the decedent’s system can be quantified by measuring the blood concentration. However, since drugs and their metabolites are present in urine longer than in blood, urine is a good reference point for what has gone on in the past and can provide clues as to how a person died. Toxicologist Kevin Shanks, FTS-ABFT recently worked on a case where a decedent’s blood only tested positive for morphine, but codeine, morphine and 6-MAM (a combined heroin marker) were present in the urine. This proves the person consumed heroin and that the morphine in the blood was the result of heroin use, not morphine use.
Conversely, a large amount of drug present in blood when nothing is found in urine can be a sign of acute overdose or rapid death. We have seen this in individuals who used heroin or were non-tolerant to drugs such as methadone and fentanyl.
The needs of an HCP monitoring patient compliance are different from those of a coroner determining cause of death. AIT recognizes these needs sometimes require a test to be customized for each service line. For instance, an HCP trying to ascertain if patients are taking their medication need a test with a lower cut-off level to identify therapeutic use than a coroner trying to determine if that same medication was a major factor in a person’s death. We have two urine zolpidem assays for this very reason. The compliance testing method has a lower cut-off level and is qualitative since a quantitative result wouldn’t be meaningful to an HCP. The forensics method has a higher cut-off and is quantitative. There is also a blood version that is open to both service lines.
Another example is our recent assay development for synthetic marijuana product K2/Spice. We developed a blood test for this in February 2011 at the request of our forensics clients that was also made available to compliance monitoring. While the blood assay was being created, however, there were a growing number of news articles about the dangers of K2/Spice, and several states were talking about making the drug illegal. Given the health dangers and increased street demand, our next goal quickly became developing a urine assay for compliance, which was completed that summer.
About R&D Project Manager Coleen Carroll, Ph.D.
Carroll joined AIT in 2009 after serving as a graduate student researcher at Indiana University, where she completed her Ph.D. in molecular, cellular and developmental biology. She previously served as an undergraduate student researcher at the University of Georgia in Athens, Ga., where she completed her bachelor's degree in genetics and graduated with honors. Carroll presented on the interpretation of compliance monitoring test results at the Midwest Association for Toxicology and Therapeutic Drug Monitoring’s annual meeting in Oakbrook, Ill. on May 4.