Call for public NMR database viewed favorably by industry experts

By Hank Schultz contact

- Last updated on GMT

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Related tags: Quality assurance, Quality control

A recent call by a formidable team of researchers for a publicly accessible NMR database was met with approval by experts in the natural products industry.

In a paper published in the journal Natural Products Reports,​ a group of prominent researchers laid out a number of examples in which mistakes can be made in the application of Nuclear Magnetic Resonance, or NMR, technology. Having a public, searchable database relating to the use of NMR for the analysis of natural compounds in dietary supplements and functional foods could lessen these errors, the authors said.

NMR details

NMR spectroscopy is an analytical chemistry technique used in quality control and research for determining the content and molecular structure of a sample. NMR can quantitatively analyze mixtures containing known compounds. For unknown compounds, NMR can either be used to match against spectral libraries or to infer the basic structure directly. 

The technique is based on the fact that many nuclei have spin and all have a charge. By applying a magnetic field, an energy transfer can be induced, and the wavelength of that transfer can be measured and analyzed to produce a spectrum. But that analysis is not completely straightforward, which is how incorrect structures can be published.

More than 70 researchers were listed as authors on the paper, included world renowned experts James McAlpine, PhD and Guido Pauli, PhD of the University of Illinois at Chicago. Researchers from across the US and Europe as well as Asia and Australia also signed on.

“A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields,” ​the authors wrote.

Applications in quality control, verification of research

Stefan Gafner, PhD, chief science officer of the American Botanical Council, said making NMR data public could go a long way toward having confidence in the published structures.

“As shown by many examples, there is an unfortunate number of erroneous chemical structures of isolates from plant, marine, and fungal materials that has been published in the peer-reviewed literature. Having the original data available would enable other researchers to have an easy means to verify a published structure, and possibly revise it if the said structure was inaccurately assigned,”​ Gafner told NutraIngredients-USA.

Gafner said that NMR is a technique still not widely used in the dietary supplement industry. One reason why is because the instruments themselves have in the past been huge — the size of a room or bigger — and very expensive.  But that’s changing, said Holly Johnson, PhD, chief science officer of the American Herbal Products Association.

“Just as the advances in DNA technology have made that more accessible to dietary supplement manufacturers, the same is happening with NMR. It used to be a million dollar experience, with instruments that had these huge magnets. Now there are bench top NMRs and it’s really about the price as an HPLC instrument,” ​she said.

Gafner said applications of NMR data is not so obvious in the dietary supplement field. It is more critical in drug discovery, where structural differences in a molecule could have profound implications for efficacy. But it does have application in the field of quality control, he said, and it could help explain why some clinical trials fail.

“The purity of the isolated compounds is often measured by HPLC-UV, which can often lead to an overestimation of the purity. Having NMR data would certainly enable researchers to more accurately determine the purity. That might lead to a re-evaluation of an active substance if later studies don’t confirm the earlier data, and may make it possible to relate the observed bioactivity to a previously (i.e., not seen in the HPLC-UV) undetected impurity,” ​he said.

Gafner said NMR data is also useful in verifying botanical reference standards, including making sure those standards haven’t changed or degraded over time. Having access to public data could allow comparisons to help detect these minor changes, he said.

Johnson said there is another key area where NMR analysis plays a role and that is in finding synthetic constituents in a product. 

“There are certain types of data that only can be gotten from NMRs. For instance, Sabinsa recently circulated a white paper on curcumin analysis and how they could detect synthetic curcumin. That is an NMR technology. It can help tell the difference between a compound that was made in a lab and one that was made in the leaf of a plant,”​ she said.

Who will verify published data?

Gafner said one question he had is if such a database were to be set up, there would still be a question about the validity of that data and how useful it might ultimately be for an industry full of small companies and limited production runs.

“Who would take the time to go back and verify the data deposited in the database? Assigning a structure based on NMR (and usually other information such as mass spectrometric data and experiments helping with the stereochemistry of a compound) can take many hours, and sometimes days, and is usually done only in cases where the compound represents a substantial commercial or academic interest,”​ he said.

But nevertheless, along with Johnson, Gafner lauded the effort.

“I think this is a great example of a transparency initiative,”​ he said.

“Just look at the author list,”​ said Johnson. “Guido Pauli is like a legend in this industry;  he took over the center in Chicago from Norman Farnsworth.  James McAlpine has done a lot of work on updated methods in the USP monographs. This long list of experts came together to say that we need to have access to this data.”

Source: Natural Products Reports
“The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.”
2018 Jul 13. doi: 10.1039/c7np00064b; erratum Nov 23
Authors: McAlpine JB et al.

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