shutterstock_192399458Recent headlines of opioid overdose deaths are shining a spotlight on the deadly crisis of addiction to opioid pain killers. Synthetic drugs such as fentanyl are not only easier to manufacture by clandestine drug labs, they are being modified to increase their effect and stay ahead of drug enforcement and detection efforts.

History of Fentanyl

Fentanyl is a synthetic opioid, originally created by pharmaceutical companies for prescription use, and more recently by clandestine labs. Doctors consider this synthetic opioid one of the strongest pain relievers, reserved for treating severe debilitating pain or for terminally ill cancer patients. A typical dose of aspirin is approximately 100 micrograms, while just 0.25 micrograms of fentanyl can cause respiratory arrest and death.  Since fentanyl is so potent, smaller amounts can be manufactured and shipped, making it easier to transport and elude drug interdiction. It has become favored by drug cartels, since it’s easier and cheaper to manufacture than heroin, which requires land for growing poppies and labor for harvesting and processing opium. According to law enforcement agencies, most of the illicit fentanyl is manufactured in China, with smuggling routes through Mexico to the United States and Canada.

Why Fentanyl?

Two pounds of fentanyl purchased in China for $3-5 thousand turns into $1.5 million on the street. Drug cartels spike heroin with fentanyl to boost their profit margin and garner more addicts with a stronger high. It’s a sinister business decision that has flooded the streets with deadlier opioid drugs, and caused more overdose deaths than ever before.

The “New Heroin” Epidemic

North America has been hardest hit by the influx of fentanyl, leading to what some are calling the “New Heroin” epidemic. Areas hardest hit in the US (Northeast, Mid-Atlantic and Southern regions) had higher rates of overdose from fentanyl in 2015, compared to heroin. Many addicts in New York prefer the cheaper and stronger drug, despite the higher chance of death. Fentanyl drug seizures in the U.S. increased from 618 in 2012 to 4,585 in 2014, an increase greater than 740% in just two years. Canada has seen its own rapid increase in fentanyl overdoses, resulting in public health emergency declarations and legislation to help counter the effects of fentanyl throughout the country. British Columbia was the first province to take action, worried that 200 deaths in the first 3 months of 2016 could become 800 by the end of the year. While the U.S. leads fentanyl overdoses globally, recent trends in Europe indicate heroin and other naturally-derived opiates to be more prevalent there (UNODC, page 47).

Reports from the Centers for Disease Control and Prevention (CDC) have been tracking the rise in opioid drug overdose, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin) from 2000 to 2014 (MMWR, page 1378). Data from a December 2015 CDC report included 61% of all drug overdose deaths (approximately 28,647) involved some type of opioid pain killer. The largest increase in the rate of drug overdose deaths involved synthetic opioids such as fentanyl, which nearly doubled from 2013 to 2014. This sharp increase in deaths involving synthetic opioids coincided with increased availability of fentanyl on the street.

Why Is Fentanyl So Elusive?

The illegal trade of fentanyl has evolved to stay ahead of drug detection and import/export laws. Since the initial laws banning export, import, and sale of fentanyl went on the books, other synthetic opioids related to fentanyl are beginning to make their way onto the streets. Illicit drug manufacturers can readily change the chemical structure of synthetic opioids. These new drugs are similar in structure to fentanyl and provide similar euphoric and toxic effects. However, since their molecular structures are not exactly the same as fentanyl, they are not readily detected by existing drug screening or forensic toxicology testing protocols like immunoassays or conventional mass spectrometry. Analogs such as acetyl fentanyl were technically considered legal to sell on the streets, until law enforcement added the drug structure to the Schedule list of illegal drugs. Multi-agency and international cooperation resulted in China banning over 116 synthetic drugs for export during the fall of 2014. Furanyl fentanyl was recently identified as one of the newest fentanyl analogs responsible for an overdose, though as of April 2016 it was not yet listed on the Schedule database. Keeping up with the constant introduction of new illicit fentanyl analogs will remain a cat-and-mouse game to maintain effective drug interdiction and detection efforts.

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A Better Solution

Current forensic drug testing methods are reliable for detecting and identifying drug substances you know you want to test for (a.k.a. targeted screening). A two-part testing process includes screening for a large number of substances, followed by a more selective laboratory assay to confirm the identity of the specific drug(s). However, each step can take 2-3 days to analyze samples for a single case, and often contributes to delays in casework turnaround times, approaching several weeks and months, according to the College of American Pathologists. Delays are further exacerbated when unknown or multiple drug substances are potentially involved in a case, perhaps requiring re-running samples and increased analysis. Law enforcement has been looking for better detection solutions which are capable of rapidly identifying new synthetic illicit drugs (eg. fentanyl analogs, designer drugs, and synthetic cannabinoids).

Since the 1950s, conventional mass spectrometry (MS and tandem-MS) has been used in forensic drug testing. However in the last 5 years, the utilization of High-Resolution Mass Spec (HRMS) technology has given law enforcement a leg up on this complex problem. This technology streamlines the testing workflow for screening and confirming the identity of known and unknown drug substances. Systems such as the Thermo Scientific Q Exactive Focus Hybrid Quadrupole-Orbitrap high resolution accurate mass spectrometer accurately identify specific, known drug substance(s), retrospectively re-investigate the same data set for newly added or unknown drugs, and provide additional data like the quantitation of drug(s) in the sample. Existing high resolution mass spectral data libraries are easily and routinely updated via cloud-based applications, reducing sample-to-answer time significantly. This means that targeted and unknown drug identification may be completed in several days versus several weeks.  New fentanyl analogs or various drug substances can readily be investigated in data from previously-run samples. HRMS systems such as the Q Exactive Oribitrap MS are the extra boost that law enforcement agencies need to stymie the epidemic of synthetic drugs like fentanyl.

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Publication:  Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching.

Publication:  Simultaneous quantification of Δ(9)-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol and cannabinol in oral fluid by microflow-liquid chromatography-high resolution mass spectrometry.

Application note:  Quantitation of Opiates in Urine Using High Resolution Mass Spectrometry