If you are leaving for a beach trip, there are essentials you pack first—chief among them a bathing suit, towels and sunscreen. While chairs, a cooler and wagon would be nice, you could do without.
If you’re equipping a forensic laboratory from the ground up, you know there’s two pieces of essential equipment—a DNA sequencer and a mass spectrometer. A mass spectrometer’s ability to identify and categorize unknown compounds is absolutely vital in today’s forensic laboratories, especially as the U.S. contends with a drug epidemic that sees dealers routinely changing the chemical formula of illicit substances to avoid detection.
As one of the largest commercially available databases, scientists routinely rely on the NIST Mass Spectral Library to identify these illicit substances. Luckily, that just got a little easier with the library’s 2020 update that sees the addition of more than 14,000 human and plant metabolites, including over 40 new fentanyl analogs.
“This new release contains 6,000 human metabolites, 8,000 plant metabolites, 2,000 drugs, 1,000 pesticides and 1,000 lipids,” Sara Yang, a NIST computational biologist who worked on quality control of the library, told Forensic. “These compounds will be greatly helpful for identifying metabolites, drugs and contaminants in pharmaceutical, medical and environmental studies.”
In addition to new fentanyl analogs, the update has added additional synthetic opioids, synthetic cathinones and amphetamines, as well as their metabolites. It also includes hundreds of other licit and possibly illicit drugs and their metabolites.
One of the biggest challenges of updating the NIST Mass Spectral Library is adding compounds that will actually help scientists make a difference. So, of the countless compounds out there, which ones should be included in the library update?
The answer to that question lies partially in Tytus Mak’s court. Mak, a NIST biostatistician, scours the catalogs of chemical manufacturers and lists of important compounds published by private companies, government agencies and scientific researchers. He then prioritizes the compounds based on their relative importance and the cost of purchasing samples for analysis.
“One of the biggest limitations in our library building process is being able to acquire the compounds that people care about. Well over half the compounds that I find in the databases that I sift through are simply not commercially available, and thus cannot be included in our library,” Mak told Forensic.
This is an even harder task in the forensic world, where the compounds are ever-changing and drug dealers are not readily sharing their compound list. When Mak comes across an analog that cannot be identified just yet, he places it in NIST’s “annotated recurrent unknown spectra (ARUS)” library.
“ARUS contains spectra for compounds that cannot be identified, but are acquired frequently and regularly enough that we have built a library of them to be identified in the future,” Mak explained. “It is indeed a difficult task as we have two unknowns, i.e. we don’t know what the compound is, and even if we did, we don’t have a spectrum for it. We’re making solid progress in developing algorithms for extracting chemical properties from unknown spectra, which give us some idea of what it could be.”
In addition to this future-proofing, in 2018 NIST developed a hybrid search algorithm that enables similar compounds to be found even when there isn’t an exact match in the library. For example, a forensic chemist can run a fentanyl analog not yet in the database through the search algorithm and receive a result of all compounds with a similar chemical structure.
To create a new analog, illicit chemists change some of the atoms in the molecule while leaving the core structure intact. This almost always changes the compound’s fingerprint by shifting some of the lines in the mass spectrum.
“Our algorithm corrects for those shifts, so you can find related compounds,” said Stephen Stein, a NIST research chemist who oversaw the development of the algorithm, and is also the lead on the Mass Spectral Library project.
With nearly 1.5 million spectra currently, the NIST Mass Spectral Library will only increase as chemists and other scientists discover, develop and identify more and more compounds—some for the betterment of society, some not.
Photo: NIST research chemist Kelly Telu injects a sample into a mass spectrometer. Credit: M. Delorme/NIST