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