When chemists need to identify the molecular components of a
sample, they turn to mass spectrometry. After blasting said sample with electrons—shattering the molecules into fragments—the
technique sorts the fragments by their mass, ultimately producing
a mass spectrum. Then, the mass spectrum is run against a database in search of an identifying match.
But what happens when a researcher can’t find a match, or a
match is just one inert group away but doesn’t register on the hit
list due to its initial differences? This is increasingly becoming a
problem for laboratories, especially those in the forensic industry
who are left to deal with the growing opioid crisis.
Last year, NIST (National Institute of Standards and Technology) released the latest version of its widely used Mass Spectral
Library, adding molecular fingerprints from more than 25,000
compounds, bringing the total number to over 265,000.
This June, at the American Society of Mass Spectrometry
(ASMS) conference in San Diego, NIST will present four posters
on its upgraded library and—more importantly—its brand new
Hybrid Similarity Search, which makes it significantly easier to
spot designer drugs and their analogs.
Hybrid similarity search function
Illicit chemists are constantly cooking up new forms of designer drugs, each with a slightly different chemical structure,
to stymie law enforcement and provide users with an enhanced
high. There’s perhaps no better example in recent memory than
fentanyl—a powerful opioid, intended as pain medication, that is
fueling the nation’s opioid crisis. Fentanyl, which can be 50 times
more potent than heroin, became the most widely used synthetic
opioid in 2017.
To control fentanyl, chemists need to identify it. But that can
be a hard task with the many kinds of fentanyl analogs that exist,
many of which are not in the chemical and/or mass spec databases yet. This is where NIST’s hybrid search comes into play.
The search function can reliably identify compounds—even
if they are not in your library—that differ from your library
compound by one chemical group that doesn’t affect the frag-
mentation. So, if you search for one compound, you will find all
the compounds that have a similar chemical structure. Thus, if
you have even one fentanyl in your library, you can theoretically
identify hundreds of analogs using the search function. More
often than not, the difference between an original designer drug
and an analog is just one inert group, like a methyl group or a
hydrogen with fluorine.
“With the hybrid search, we use two different kinds of
peaks within the mass spectrum—one for the ions and one for
the neutral losses,” explains Stephen Stein, the NIST research
chemist who oversaw the development of the search algorithm.
“By combining them together, you can use both criteria to do
the matching and find spectra in the library. As a result, you are
finding a lot more compounds, especially compounds where the
molecule you are looking for differs from a library compound by
one inert structural unit. That could appear either in the ion or
the neutral loss. Wherever it appears, it will find the compound
in the library by having that additional information.”
The method works for a large fraction of drugs of abuse, in-
cluding synthetic marijuana, bath salts and other designer drugs.
But, it’s not limited to the forensic industry. The search func-
tion can be used as a general tool for finding analogs of other
compounds, which are present in nature, in urine, in biological
samples, etc. According to Stein, the method finds applications in
diagnosing medical conditions, identifying environmental pollut-
ants, developing new fuels, cutting-edge metabolic research and
the flavor and fragrance industry.
“If you use it, it finds all the same hits it would find if you
didn’t use the hybrid search, but it adds to the hit list everything
else that matches with the mass,” Stein told Laboratory Equip-
Mass Spectral Library
Gets Automation Upgrade
NIST has updated its popular spectral library with a hybrid search
function designed especially to help with the nation’s opioid crisis.
by Michelle Taylor, Editor-in-Chief
The mass spectrum for the synthetic opioid, fentanyl. Photo: NIST