CEO SUMMARY: Researchers at the University of Colorado in Aurora used mass spectrometry technology to create a paradigm-shifting toxicology test. It uses a urine specimen and can identify 112 compounds and more than 500 illicit and brand-name drugs in a single assay. For pain management testing, not only does this bend the cost curve downward, but the multiplex test gives physicians a more accurate way to screen patients for therapeutic drugs and drugs of abuse.
MULTIPLEXED MASS SPECTROMETRY IS POISED to trigger a revolution in clinical laboratory testing. Advocates of this technology point out that, for certain types of lab tests, multiplexed mass spec can produce a more precise answer and do so at considerably less cost than many existing lab test methodologies.
One innovative use of this technique for clinical purposes can be found at CU Toxicology of Aurora, Colorado. It has developed a multiplexed mass spectrometry test that can identify 112 compounds and more than 500 illicit and brand-name drugs at a price that can be disruptive to the existing standard of practice in pain management testing.
CU Toxicology is a nonprofit lab that is part of a public-private partnership with the University of Colorado School of Medicine’s Department of Anesthesiology. The CLIA-licensed and CAP-accredited laboratory is on the CU Anschutz Medical Campus in Aurora, Colorado.
The use of a multiplexed mass spec approach for therapeutic and drugs-of-abuse testing is the brainchild of Jeffrey Galinkin, M.D., Chief Medical Officer of CU Toxicology. He is also a professor of anesthesiology and pediatrics at the University of Colorado School of Medicine.
“This assay tests for 112 drug compounds at once,” stated Galinkin, in an interview with THE DARK REPORT. “In a urine sample, it can find virtually any substance in just about any quantity. The test is far more sensitive and specific than traditional ELISA-based urine drug testing.”
Disruptive Innovation
CU Toxicology’s mass spec test—capable of identifying 112 compounds and more than 500 illicit and brand-name drugs in a single assay—is a disruptive innovation. Galinkin believes that many labs may be reluctant to adopt this methodology because such a test could cut into revenue traditional testing methods generate.
CU Toxicology prices this test at $200 for a single individual. The lab negotiates lower prices for more volume.
“Most laboratories doing urine drug testing make a lot of money off the current testing methodologies because they can bill for the initial screening up front and then separately bill for each confirmation test,” observed Galinkin. “Depending on which drugs a lab or a referring physician is trying to identify, the cost of conventional testing could range from $800 or $1,600. Our proprietary multiplexed mass spec test can do the same job for a fraction of that cost by screening for 112 drugs all at once.”
Primary, Secondary Uses
The assay has two primary applications in toxicology. One application is to support pain management clinics. The other use is in support of addiction treatment centers.
“Also, here in Colorado, we have emergency departments using this assay to identify the drugs an unresponsive patient suffering an overdose may have taken,” commented Galinkin. “employers and health plans can use the test to verify patient compliance with prescribed medications and to detect misuse of prescription or illicit substances.
“We have solved a difficult problem,” Galinkin said. “For the 112 chemicals on our list, we can say with certainty which drugs every patient has been taking or not taking, based on the results of our multiplexed mass spectrometry test.”
The typical toxicology lab will use an ELISA-based test as an initial screen. “These tests are about 60% to 70% sensitive,” explained Galinkin. “Next, labs use mass spec or a radioimmunoassay— depending on the lab—to confirm the presence of the drugs identified in the initial screen. The problem with this combination testing is the traditional tests have a much higher detection limit than we do.
“The much lower detection limit of our assay allows us to identify very small quantities of a drug in a patient’s system,” he said. “The high sensitivity levels allow us to identify drugs that normally slip through with industry-standard drug screens.
“In addition, we can identify and confirm more than 500 prescription and over-the-counter drugs,” added Galinkin. “This is important when trying to manage patients taking multiple drugs.
“This aspect of our test is significant for polypharmacy, or the use of multiple drugs at once,” continued Galinkin. “Polypharmacy is an epidemic in this country. More than one in five U.S. citizens now use three or more prescription drugs, and more than one in 10 use five or more prescription drugs.”
The benefits of the multiplexed mass spec assay were important to laboratory professionals at Kaiser Permanente Colorado in Denver, according to Michael Sheehan, Ph.D., the Technical Operations Manager for Kaiser’s central laboratory.
Sheehan stated that, previously, Kaiser’s central lab had sent all urine drug testing work to one of the national lab companies. However, in order to save money and reduce turnaround time, it had internalized much of that work.
Confirming Positive Results
“After we started doing our own initial drug screens, we needed a process where we could confirm a positive result that we hadn’t expected to be positive,” said Sheehan. “We also wanted to confirm a finding about a drug that was supposed to be there but wasn’t. Further, because we’re an HMO, there is a cost associated with everything our lab does and we don’t get reimbursed for each test we run.
“Our drug screens were developed based on consultations with our client clinics,” he noted. “Currently, for dependency clinics and pain clinics, our lab runs a screen for seven drug classes. Those seven classes are amphetamines, benzodiazepines, cocaine, methadone, opiates, THC (or delta-9-tetrahydrocannabinol), and oxycodone.
“It is important to note that, here in Colorado, Kaiser does not have any hospitals,” said Sheehan. “Thus, our lab does not need to do any toxicology screens for the emergency room.
“There are two benefits from the CU Toxicology testing that are extremely useful for us here at Kaiser,” he continued. “The first benefit is that we can screen down to a level that is extremely low. The level is so low that it’s actually below the threshold for detection with more traditional testing.
More Precise Detection
“The detection level of CU’s mass spec-based toxicology screen is about 10 to 30 times lower than we can detect with our lab equipment,” stated Sheehan. “To say whether a test is positive or not, CU Toxicology can go down to 5 to 10nanograms per milliliter. By contrast, our lab can go down to only 100 to 300 nanograms per milliliter.
“The second benefit for us involves the chemical dependency clinics that are helping patients get off of opiates,” he explained. “Those patients now are on suboxone, which cannot be detected by our seven drug screening panel.
“That means the chemical dependency clinics don’t know if the patients are compliant or if they are diverting the drug to a family member or someone else,” stated Sheehan. “However, we can send that test for confirmation to CU Toxicology, where it can easily detect if it is present or not.
“Another advantage for us in working with CU Toxicology is that their test can detect traces of illicit drugs (such as cocaine and methamphetamine) up to one month post ingestion, whereas our screen would be negative in three to five days,” he noted. “This gives our clinics a better picture of whether their patients are compliant with their non-drug regimens.
“This level of detail cannot come from traditional toxicology testing, yet that information is critically important for these clinics,” Sheehan explained. “These are the clinical advantages of having a toxicology screen that is highly sensitive and specific for pretty much any drug a patient might be able to obtain.”
For Sheehan, it was important to manage the cost of toxicology testing in appropriate ways. “Take the example of testing someone for amphetamine use,” he said. “If I send that test to a national lab, it would cost us $45; and all I would know was whether or not the patient was taking an amphetamine-like drug. If I sent that one test to CU Toxicology, that would cost us $115, but I would get the patient’s complete drug history as well.
Benefits of Multiplex Assay
“Thus, for a single test, the CU Toxicology pricing is not always the first choice,” he continued. “But if our lab needs to test for two, three, or multiple drugs at once— which is more often the case—then the Cu Toxicology price of $115 is very good. And it is certainly more efficient to order one test and cover any and all drugs that need confirming rather than piecemeal testing.”
Multiplex testing is becoming more important in toxicology, Sheehan added. “That ability to economically screen for many drugs simultaneously is very important for addiction treatment,” he said. “That is because those patients sign contracts saying they won’t take anything while they’re in the clinic; and we know that they are compliant out to a month rather than the three to five day period that we would get with conventional testing.
“Using CU Toxicology’s multiplexed mass spec method, which is confirmatory testing, thus gives our ordering physicians a one month drug history window, rather than only a week’s look, which is uniquely important with respect to managing these patients,” concluded Sheehan.
Pain Management Doctor Saw Potential in Using Mass Spectrometry for Toxicology Screens
IN 2011, RESEARCHERS at the University of Colorado were seeking to develop a mass spectrometry assay to identify athletes using performance-enhancing drugs.
At the time, Jeffrey Galinkin, M.D., was a professor of anesthesiology and pediatrics at the University of Colorado School of Medicine. In this role, he recognized that it would be relatively easy to adapt mass spec technology for toxicology screening.
“At that time, we referred our tox screens to an outside laboratory and it took weeks to get the results back,” said Galinkin, who is also the Chief Medical Officer of CU Toxicology. “Moreover, the lab test results we got back never seemed to correlate with what the patients were taking.
“I saw that, by developing mass spectrometry for toxicology testing, we could do something that could literally change the industry,” recalled Galinkin. “Market research showed that toxicology was a much bigger industry opportunity than sports screening for performance-enhancing drugs.
“From there, it took us two years to find the right mass spectrometry instrumentation,” he continued. “We selected the QTRAP 5500 System manufactured by AB Sciex. We now have three of them. We also needed to develop our own proprietary software to manage the many points of data we were getting from the mass spec.
“Today, our three machines at CU Toxicology run 24/7 and our throughput is variable,” stated Galinkin. “We currently do about 50 to 100 tests per day but we have the capacity to do about 1,000 tests per week.”
On staff are four toxicologists and there are no pathologists. CU Toxicology’s turn-around time is between 24 and 48 hours.
“We believe this is an important technology because the mass spec can weigh every compound in the sample every time,” noted Galinkin. “Each time one of these compounds comes through, we know—based on the mass spec—the specific drug and the quantity of that drug.
“This high level of confidence is very different from traditional lab testing technology used in toxicology today,” he concluded. “The accuracy of our multiplexed mass spec test delivers an important clinical benefit. It allows an addiction clinic or a pain management center to build trust instantly between a client and patient. Our multiplexed mass spec assay changes the whole idea about patient/physician trust because the toxicology screen can’t be fooled.”
Multiplex Mass Spec Test Finds Elderly Drug Dealer
NO ONE EXPECTS TO FIND A DRUG DEALER among the residents of an assisted-living facility. But that’s just what a Colorado toxicology lab uncovered recently when it used its new multiplexed mass spec urine drug test.
When the test result came back positive for cocaine, the administrator called the lab saying there must be a mistake. The patient was a little old lady, a most unlikely cocaine user, the administrator said.
So Jeffrey Galinkin, M.D., Chief Medical Officer of CU Toxicology and professor of anesthesiology and pediatrics at the University of Colorado School of Medicine, retested the patient. The retest confirmed the first result. There was no mistake, Galinkin said. The patient had tested positive for cocaine, he told the administrator.
Upon further investigation, the center learned that the woman had been dealing cocaine in the facility and using the drug herself, Galinkin reported.
The drug-dealing little old lady was nabbed because CU Toxicology uses an assay that tests for 112 drug compounds at once. In a urine sample, it can find virtually any substance in just about any quantity. The test is far more sensitive and specific than traditional ELISA-based urine drug testing, Galinkin told THE DARK REPORT.
