Lab Matters Spring 2020 - Page 24

INDUSTRY MATTERS Meeting the Needs of Opioid Biosurveillance By Joseph Clarke, BSc, Waters Corporation and Michelle Wood, PhD, Waters Corporation On a global level, overdose deaths due to opioids have increased dramatically over the past several years. In North America, the situation has been particularly challenging with almost 450,000 people dying from overdoses involving opioids, (prescription and illicit preparations) from 1999 to 2018. Since 2013, there has been a significant increase in overdose deaths involving synthetic opioids such as fentanyl. Over this same period, drug enforcement agencies reported significant increases in seizures of illicitly manufactured fentanyl, and most of the recent overdose cases are believed to be due to illegal, rather than pharmaceutical, fentanyl. The last decade has also seen the clandestine synthesis of an everincreasing number of “designer” fentanyls. Chemical derivatives are produced by modification or substitution of various functional groups of the fentanyl molecule to produce new, untested drugs that are intended to mimic the effects of traditional drugs, but are often significantly more potent. Although we have heard much about fentanyl and its analogs in recent times, current data suggest that modified versions of other synthetic opioids, such as the benzimidazole class, are the latest emerging threat. Identification of fentanyl and other synthetic analogs is crucial in alerting public health authorities to potential overdose risks. However, the variety, number and concentration of potential compounds in a sample can present a considerable challenge to traditional analytical techniques (e.g., cross reactivity of analogs to immunoassay is highly variable). Even certain mass spectrometry techniques, such as tandem mass spectrometry (MS/MS), will be challenged to keep up with emerging novel drug substances, since they rely on the availability of certified reference material (CRM) in order to determine the appropriate detection parameters for the new drug, which may not be readily available. UNIFI TM screening system software A New Solution High-resolution mass spectrometry (HRMS) surpasses the limitation of low-resolution analyzers through the determination of substances and their metabolites with high mass accuracy. Importantly HRMS imparts the ability to screen for new drug molecules without the requirement for CRM, as detection is based on the exact mass of a molecule and the isotopic pattern. As such, the chemical formula of a compound can be confirmed or even ascertained. Waters Corporation has developed a comprehensive screening system that incorporates ultra-performance liquid chromatography (UPLC) coupled with HRMS. The benchtop Xevo ® G2-XS QTof [Quadrupole Time-of Flight] detector is combined with a powerful software–UNIFI ™ . Laboratories do not have to spend valuable time developing and optimizing chromatography and mass spectrometry methods or trying to analyze complex data. The Waters Forensic Toxicology Screening Application Solution provides all required analytical methods for targeted and non-targeted (discovery) screening workflows. Targeted analysis compares acquired data with a comprehensive library for known, characterized drugs/analogs; the UNIFI scientific library contains data for hundreds of substances. The Xevo G2-XS QTof (Quadrupole Time-of Flight) For new analogs or new psychoactive substances for which very limited information is available, UNIFI includes powerful investigative tools to aid identification, and highlights any components that have not been identified using the scientific library for further investigation with discovery tools. The elemental composition of the component or components under investigation is automatically calculated and searched against online libraries and databases using both precursor and fragment ion data. In silico fragmentation, provided as a standard tool, can aid this investigation by using molecular structure to generate theoretical fragments and assign plausible or likely structures to the observed ions. These structures can then be added to the library for future investigations. n Waters is a Platinum Level sustaining member of APHL. 22 LAB MATTERS Spring 2020 PublicHealthLabs @APHL APHL.org