NEW YORK (360Dx) – As the number of deaths resulting from fentanyl continue to climb, Pacific Toxicology Laboratories is responding by expanding its test menu to enable doctors to treat their patients for substance abuse linked to the potent opioid.
Over the past year or so, an alarming number of deaths has been blamed on overdoses from fentanyl, a fast-acting synthetic opioid, and its analogues. Deaths in the US linked to synthetic opioids, mostly fentanyls, have risen to more than 20,000, Pacific Toxicology said, citing US Centers for Disease Control and Prevention data. Meanwhile, the use of fentanyl and its analogues rose by more than 500 percent from 2014 through 2016.
A CDC morbidity and mortality report published in April further reported that 82 percent of fentanyl overdose deaths involve illegally manufactured fentanyl and fentanyl analogues, while 4 percent of the overdoses originated from legal prescriptions, and 14 percent involved an unknown source of fentanyl.
What's most alarming is the rise in opioid overdoses in the latter half of 2016, which showed that 70 percent of opioid overdose deaths resulted from fentanyl and fentanyl analogues, Jeff Lanzolatta, CEO and part owner of Pacific Toxicology Laboratories, a CLIA-licensed lab based in Los Angeles, said in an interview.
The laboratory provides drug testing, biological monitoring, and medical surveillance among other laboratory services, and recently expanded its menu to include tests for drugs such as fentanyl. According to Lanzolatta, Pacific Toxicology's R&D team is also working to include "as many of the analogues as we can … into our testing panels."
The laboratory now routinely screens and quantifies the presence of several fentanyl analogues in urine samples, including butyryl fentanyl; n-phenyl –1– 4 – piperidianamine; furanyl fentanyl; ocfentanil; acetyl fentanyl; alfentanil; remifentanil; sufentanil; valeryl fentanyl; para-fluorofentanyl; (+/-) cis- 3- methyl fentanyl; carfentanil; and nor carfentanil.
"In the drug testing sphere, with the amount of attention being drawn on the opioid crisis and with [the US executive branch] pointing out fentanyl as one of the bad guys, I would expect that we will see a lot more labs doing what we are doing," Lanzolatta said.
In March, the White House Office of National Drug Control Policy said that it recognized the use of illicit fentanyl and heroin as "an urgent public health crisis" that is compounding the ongoing prescription drug epidemic in the US.
A recent report published by the United Nations Office on Drugs and Crime noted that products containing fentanyl and its analogues appeared on the illicit drug market in the 1970s and 1980s, and "became notorious for accidental overdoses." The problem seems to have resurfaced "and the clandestine manufacturing of fentanyl has risen to unprecedented levels," the report noted. It said that the required materials and equipment for manufacture are readily available online, at low cost, and the situation is aggravated by the rapid emergence of novel fentanyl analogues which have not been approved for medical use.
Clinical testing laboratories such as Pacific Toxicology Laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to seek out fentanyl and its analogues in patients' urine samples.
"It's a high-complexity test through which we train the system to recognize the molecule we are looking for," Lanzolatta said. He noted that the laboratory is screening for fentanyl and its analogues down to 2 parts per billion. Although that's the current limit of detection, Pacific Toxicology is looking to push it lower. "This stuff is so potent that we have to get to it at the smallest levels that we can, so we're always working to do better," Lanzolatta said.
Fentanyl, an opioid pain medication often applied transdermally by a skin patch, is 50 to 100 times more potent than morphine. Fentanyl analogues, designed to mimic the pharmacological effects of fentanyl, can be 10,000 times more potent than morphine.
In July, the FDA, recognizing the urgency of the fentanyl issue, granted 510(k) clearance for a urine-based enzyme immunoassay produced by Immunalysis, a division of Alere, which recently was acquired by Abbott. The Immunalysis Sefria test is the first 510(k) cleared fentanyl enzyme immunoassay.
Previously, fentanyl immunoassay tests were only available for forensic testing, Immunalysis said. With its clearance, the assay is available for fentanyl drug screening in CLIA-certified reference laboratories, hospitals, physician offices and other healthcare settings that perform moderate complexity testing, the firm added.
Kathy Miller, vice president of sales and marketing at Immunalysis, said in a statement that the availability of an FDA-cleared fentanyl immunoassay "enables more reference and hospital laboratories to conduct precise qualitative screening, which is a key strategy in stemming the alarming increase in misuse and abuse of fentanyl."
She noted that the fentanyl urine drug screening test rounds out its "offering of technologically advanced assays for detecting prescription and illegal drugs of abuse by providing clinicians and toxicologists with a relevant menu of FDA-cleared opiate and opioid tests."
The immunoassay detects the presence of fentanyl in urine with a cutoff of 1 ng/mL, Immunalysis said, adding that in clinical performance studies, testing "compared favorably to liquid chromatography-mass spectrometry analysis in both sensitivity and specificity."
Alere declined a request for an interview for this article, citing business priorities related to its current integration with Abbott.
Although the Alere test was the first fentanyl enzyme immunoassay cleared by US regulators, Cortez Diagnostics also offers an immunochromatography-based, one-step test for use by healthcare professionals. Its test provides a qualitative analysis of fentanyl in human urine. The cutoff level for the test is 200 ng/ml of fentanyl.
According to Quest Diagnostics, which offers fentanyl screening and confirmatory testing, opioid drug testing includes presumptive immunoassay screens and definitive mass spectrometry quantitative analyses, as well as confirmations of presumptive positive results. Mass spectrometry is the most sensitive and specific drug testing method, the firm said.
Lanzolatta agrees. He said that the mass spec-based method should be the test of choice, adding that the cutoff level for an enzyme immunoassay that could be used as point-of-care test "doesn't get anywhere near the levels we need to reach when we're testing for fentanyl."
In a recent prescription drug monitoring report published by Quest, the company said that more than half of positive patient specimens show signs of prescription drug misuse, and nearly half of all opioid overdose deaths involve a prescription opioid.
More than 25 percent of patients monitored by lab tests for prescription drug adherence are concurrently taking both opioids and benzodiazepines, according to a new study published in the Journal of Addiction Medicine by researchers at Quest. Benzodiazepines, a class of agents that work on the central nervous system, are used in the treatment of anxiety, panic disorder, seizures, or sleep disorders.
In 2017, drug testing within the American workforce, fueled by illicit drugs, produced the highest number of positive results in 12 years, according to an analysis of more than 10 million workforce drug test results conducted by Quest and published earlier this year in its annual drug testing index.
When governments "cracked down on the ability of doctors to prescribe and patients to get" prescribed opiates, "a subset of the population that is susceptible to becoming addicted turned to black market options, and began routinely cutting drugs such as heroin with fentanyl to make it more powerful," Lanzolatta said.
He noted that there are 29 laboratories in the US certified to conduct drug testing by the Substance Abuse Mental Health Services Administration, an agency within the US Department of Health and Human Services.
He said that in the future, he hopes to see an increase in clinical testing that contributes to a decline in the prevalence of postmortem test results reflecting overdoses with opioids.
"I hope that other folks do what we have done, and if they call us we are not going to pretend that we have the recipe for Coke or Kentucky Fried Chicken. This is something that we think should be broadly available," he said.