Spotlight on: fentanyl

What is fentanyl?

Fentanyl and its analogs are members of the class of drugs known as rapid-acting synthetic opioids used for surgery, to treat patients with severe pain, or for patients with chronic pain who are physically tolerant to other opioids. Fentanyl works by binding to the body's opioid receptors, which are found in areas of the brain that control pain and emotions. Its effects include extreme happiness, drowsiness, nausea, confusion, constipation, sedation, tolerance, addiction, respiratory depression and arrest, unconsciousness, coma, and death.

Fentanyl was first developed in 1959 and introduced in the 1960s as an intravenous anesthetic. Currently, it is legally manufactured and distributed in the United States. The problem arises when licit fentanyl pharmaceutical products are diverted through theft and fraudulent prescriptions and via illegal manufacturing and distribution. Fentanyl is also illegally manufactured and laced into illicit preparations that are distributed in powder or pill form through the illegal drug market. This process is commonly used by drug dealers to make drugs cheaper, more potent, more addictive, and more dangerous. For these reasons, the U.S. Drug Enforcement Administration classifies fentanyl and some of its analogs as Schedule II prescription drugs. On February 6, 2018, a proactive temporary (emergency) class‐wide scheduling of fentanyl‐related substances was implemented based upon the fentanyl core structure in an effort to reduce the proliferation of these hazardous substances and minimize their impact on public safety.

What are the challenges with analysis by LC-MS?

As these substances are gaining popularity as substitutes to controlled opioids and are often used as cutting agents or adulterants to heroin and other commonly abused drugs, it is imperative for forensic testing laboratories to have sensitive and accurate detection methods. But fentanyl and its analogs are structurally similar, and many are isobars, creating an analytical challenge for their detection. Traditionally, fentanyl screens are either performed by immunoassay or GC-MS. Analysis by immunoassay has considerable cross-reactivity which leads to a high rate of false positives. GC-MS requires sample derivatization and lengthy chromatographic runs to accurately identify fentanyl and its analogs. As a result, forensic laboratories have implemented LC-MS as a rapid and robust method to detect analogs and/or metabolites* with a high level of selectivity and specificity. The sensitivity and precision of LC-MS provides the ability to detect low levels of fentanyl and its analogs in authentic case samples that would normally go undetected, providing a clearer picture for help in determining the cause of overdose/death.

Why is fentanyl so interesting?

As a synthetic opioid approved for treating severe pain and aiding, fentanyl has shown clear medical benefits. However, continuous abuse of fentanyl and its derived analogs has become a major public health issue. The prevalence of accidental overdose and deaths associated with illicitly-manufactured fentanyl has risen dramatically in recent years, fueling the ongoing opioid crisis. Because fentanyl and its analogs are so potent, can be made easily and relatively inexpensively in a laboratory, and very small amounts are sufficient to supply large markets, the potency per weight ratio have made it an ideal drug to smuggle.

Using LC-MS for testing fentanyl

Timely and comprehensive analytical drug screening approaches capable of detecting fentanyl and its many analogs are critically needed in the forensic toxicology laboratory. SCIEX has collaborated extensively with thought leaders and key opinion leaders in organizations such as the Center for Forensic Science Research and Education (CFSRE) and their NPS Discovery program to develop marketing content to promote the use of LC-MS to screen, characterize, identify and quantitate these substances in a variety of biological matrices. Additionally, our team of scientists have developed a variety of workflows to showcase innovative LC-MS solutions to help forensic toxicology laboratories implement those new methods. Our technical content showcases our expertise in the analysis of these substances and demonstrates the performance of our systems to confidently detect and quantify them with high precision and accuracy.

Some interesting facts about fentanyl

When prescribed by a doctor, fentanyl is administered as a shot, a patch or as lozenges that are sucked on like cough drops
The illegally manufactured fentanyl that has been associated with the opioid overdose epidemic currently ongoing in the US is generally found in powder form, spotted onto blotter paper, put in eye droppers or made into pills emulating other prescription opioids
Drug trafficking organizations typically distribute fentanyl by the kilogram.  One kilogram of fentanyl has the potential to kill 500,000 people!*
42% of pills tested for fentanyl contained at least 2 mg of fentanyl, considered a potentially lethal dose*
Despite its risks of overdose and addiction, fentanyl is in fact an important medication for managing severe pain, particularly after surgery and for advanced-stage cancer. Research is aimed at finding safer ways to use fentanyl, minimizing its potential for abuse while maximizing its therapeutic benefits
Ongoing research is aimed at identifying better antidotes and treatments for fentanyl overdose, such as the development of more effective formulations of naloxone (Narcan), a medication used to reverse opioid overdoses

SCIEX, there where it counts

Unparalleled performance: exceptional sensitivity and quantitative performance of the SCIEX 7500+ system enable accurate detection of fentanyl, its analogs and their metabolites in poly-drug, authentic case samples at trace levels that were not previously achievable
Biological insights: the sensitivity of the SCIEX 7500+ system provides a means to monitor low levels of ultra-potent fentanyl analogs in overdose scenarios, providing valuable insight into the causation of death
Screening workflow: combining optimized LC conditions and the use of the Scheduled MRM algorithm in SCIEX OS software enables robust and sensitive quantitation and identification of isobaric species with high precision and accuracy, even at trace-level concentrations