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Benchtop NMR – Screening Tool for Adulterated Herbal Supplements

by Benchtop NMR, Chemistry, Herbal Supplement, NMR

Survey of Low Field NMR Spectrometer Platforms for Successful Screening of Sexual Enhancement and Weight Loss Supplements for Adulteration with Drugs and Drug Analogs

John C Edwards1, Kristie M Adams2, and Anton Bzhelyansky2

1Process NMR Associates, Danbury, CT
2United States Pharmacopeial Convention, Rockville, MD

The adulteration of dietary supplements (or natural health products) with synthetic pharmaceuticals is an area of increasing concern, which presents substantial risk to public health. Widely available in retail and via the Internet, these products are often marketed as sexual enhancement, weight loss and/or bodybuilding supplements. Unlike prescription drugs, supplements do not require premarket approval by FDA before they are made available for public consumption. In fact, the agency can only take investigational action after the adulterated product has caused harm and the adverse event has been reported via MedWatch (FDA’s online portal for voluntary reporting of adverse events associated with drugs, medical devices and dietary supplements).
Development of analytical tools for screening and identification of adulterated products in the marketplace represents a significant step forward in the fight against adulterated dietary supplements. Several organizations, including AOAC and USP, have undertaken initiatives to evaluate and recommend analytical methodologies for screening supplements for adulteration. HPLC and mass spectrometry have so far dominated the screening and quantitation studies published in the literature, with NMR spectroscopy often relegated to the status of structure elucidation tool. In this work, we investigate the ability of several-low field NMR spectrometric platforms to successfully identify and quantify the presence of adulterating drug substances in sexual enhancement and weight loss supplements purchased online and in US retail. 1H qNMR of both types of samples was performed with 300 MHz NMR to confirm the presence of adulterants such as sildenafil, tadalafil, and their structural analogues (sexual enhancement supplements) and various synthetic stimulants (weight loss supplements). We have concluded that a simple sample preparation protocol combined with straightforward 1H NMR spectroscopic analysis yields a rapid, robust and reliable screening test for adulterated supplements, presenting an attractive alternative to more labor-intensive, expensive and expertise-demanding techniques du jour.

This was presented by John Edwards at SMASH in September 2014, and at the Carolina NMR Symposium in November 2014

presentation can found here: Benchtop NMR – Herbal Supplement Adulteration Screening

43 MHz - 1H NMR - Benchtop Analysis of Contamination of herbal supplements with PDE5 inhibitors
43 MHz – 1H NMR – Benchtop Analysis of Contamination of herbal supplements with PDE5 inhibitors
300 MHz - 1H NMR - Benchtop Analysis of Contamination of herbal supplements with PDE5 inhibitors
300 MHz – 1H NMR – Benchtop Analysis of Contamination of herbal supplements with PDE5 inhibitors

From Atoms to Flavour: The Chemistry of Beer

by Beer, Chemistry, Chemometrics, NMR, Process NMR, qNMR, Reaction Monitoring Tagged: , , , , ,

Adam DiCaprio (ex PNA) gave an excellent Science Cafe Talk under the auspices of the ACS North Carolina Section at the Busy Bee Cafe in downtown Raleigh on December 2, 2014. CHanging gears from his previous talks he centered the discussion on malt and hop chemistry as well as an start-to-finish NMR analysis of production runs of a bottled commercial tavern ale. If you are interested in having Adam give a detailed chemistry seminar on beer at your section meetings please contact him directly at adam@process-nmr.com.

A PDF version of his talk is available here …. ACS Science Cafe Talk – Dicaprio – Busy Bee Cafe – Raleigh NC – 12-2-14

Comparison of 1H NMR Spectra Obtained at 42, 60, 82, and 300 MHz – Fish Oil Omega-3 Ethyl Ester Supplement Example

by Benchtop NMR, Chemistry, Chemometrics, NMR, PAT, Process NMR, qNMR

Process NMR Associates is currently developing NMR applications based on direct measurement of chemometric modeling on NMR data obtained on numerous NMR platforms. Our intention is to develop solutions that can be executed on any NMR platform. With this in mind we are currently developing a fish oil analysis application that can provide the EPA and DHA omega-3 fatty acid content of fish oil supplements manufactured by an ethyl ester esterification process. We have obtained data at 42 MHz, 60 MHz, 82 MHz and 300 MHz. The chemometric modelling yielded PLS models for all 4 field strengths that yield effectively the same result – DHA can be measured to +/- ~1.1 wt% and EPA can be measured to +/- ~2.2 wt% by a 40 second 1H NMR measurement. THe correlation is derived from a  regression of the 1H NMR variability with primary GC analysis values.

This analysis has been shown for the 300 and 60 MHz data in a previous post on this blog. The same analysis was also obtained, with similar results, on 42 and 82 MHz platforms proving that individual applications can be automated and provided at all relevant frequencies of NMR analysis whether on superconducting lab systems or permanent magnet benchtop systems.

At each field strength the relative lineshapes are pretty much the same (<1 Hz at half height). The field strength differences mean that the same spectrum is dispersed across frequency space proportionate to the magnetic field. Figure 1 below shows the frequency space spectra obtained at all 4 field strengths on the same sample.

Figure 2 shows the same spectra displayed on the usual normalized chemical shift scale (ppm). In these spectra the data is stretched in order to allow the chemical shift comparison of the data. IN effect the 42 MHz NMR is stretched by a factor of 7, the 60 MHz data by a factor of 5 and the 80.2 MHz data by a factor of 3.7. The effect of the relative size of J coupling compared to the frequency space occupied by 1 ppm is an interesting observation to see directly. In traditional NMR analysis the resolution of various peaks was always the driving force for increasing the magnetic field strength of NMR instruments. With todays powerful PC’s and advanced software information can be garnished readily from any of these spectra by way of global spectral deconvolution or multivariate statistics.It is no longer necessary to obtain baseline resolution in order to integrate a resonance and obtain quantitative information.

THough the data is more closely packed together in the low field spectra it can be acknowledged that the same information is present in all 4 spectra. Automation approaches can be developed that will allow accurate measurement of quality parameters, component quantification, or structural verification to be performed on data obtained from any of these NMR systems.

The development of readily deployable NMR benchtop systems at an affordable price point must surely lead to the development of NMR into a more widely utilized technique outside of the realms of scientific study and quality control that NMR has thus far been involved.

1H NMR at 42, 60, 82, and 300 MHz
Figure 1: Comparison of 1H NMR spectra obtained on an omega-3 fish oil supplement obtained at 42, 60, 82, and 300 MHz displayed in frequency space. These spectra show the native spectra dispersion obtained at the different magnetic field strengths of the NMR spectrometers
CHemical SHift Scale Normalization of 1H NMR spectra obtained on the same sample at 42.5, 60.3, 82.3, and 300 MHz
Chemical Shift Scale Normalization (ppm) of 1H NMR spectra obtained on the same sample at 42.5, 60.3, 82.3, and 300 MHz. In these spectra the absolute frequency of the spectrum is divided by the spectrometer frequency to obtain a normalized spectrum where the chemical shift in ppm of the various peaks in the spectrum are observed at the same position on the ppm NMR scale. In this normalized view the relative proportion of a ppm that the J couplings represent in the 1H multiplets can be plainly seen.  

 

 

 

 

Presentations at SMASH 2014

by Beer, Chemistry, Chemometrics, Herbal Supplement, Process NMR, qNMR, Reaction Monitoring

“Beer Manufacturing and Analysis by NMR”, John C. Edwards and Adam Dicaprio, Presented at the Mestrelab MNova Users, Meeting – SMASH, Atlanta, GA, September 7, 2014
Get PDF Here

“Survey of Low Field NMR Spectrometer Platforms for Successful Screening of Sexual Enhancement and Weight Loss Supplements for Adulteration with Drugs and Drug Analogs”, John C. Edwards, Kristie Adams, Anton Bzhelyansky , Presented at SMASH Conference, Atlanta, GA, September 7-10, 2014.
Get PDF Here