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

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.  

 

 

 

 

Agilent drops a bombshell – big changes are coming for the NMR community

Agilent Technologies to Close Nuclear Magnetic Resonance Business

SANTA CLARA, Calif., Oct. 14, 2014

Agilent Technologies Inc. (NYSE: A) today announced it is exiting its Nuclear Magnetic Resonance business. Agilent entered the NMR business in 2010, with the acquisition of Varian. Since then, the business has not met growth and profitability objectives.

“Today’s announcement represents a difficult decision necessary to drive improved profitability,” said Mike McMullen, president and chief operating officer, and CEO-elect. “The NMR team has been extremely dedicated and has made many excellent contributions. However, this action is a step in ensuring that our investments are placed on higher-value life sciences, applied markets and diagnostics solutions that will continue to drive growth across the company.”

Agilent will stop taking new NMR system orders immediately, but the company will continue to meet customer commitments for orders in progress and for ongoing support contracts. Agilent will continue to provide service on all installed NMR systems.

The company expects that this decision will eliminate about 300 jobs, mostly within the next 12 months. The majority of the affected positions are located in Yarnton, U.K., and Santa Clara, California.

Today’s announcement is part of Agilent’s strategy to address the business shortfalls of its Research Products Division. In early 2013 Agilent announced its exit of the OEM and Specialty Magnet business and later the MRI business to focus resources on the core NMR portfolio. Despite these adjustments, the NMR business has continued to fall short of growth and profitability objectives.

To cover the cost of exiting this business, Agilent will take an approximate $72 million restructuring charge in the fourth quarter. It expects a $20 million to $30 million decline in revenues in fiscal year 2015 due to the NMR business closure, but a positive impact of about $10 million in operating profit in FY15.

For the fourth quarter of 2014, Agilent anticipates non-GAAP earnings per share of $0.87 to $0.91, and projects revenues to be negatively affected by currency at about $13 million, and lower NMR-related revenues by about $12 million.

Keysight has posted its investor roadshow slide deck on its website at www.investor.keysight.com. “New Agilent” will post its investor roadshow slide deck on Friday, Oct. 17, after the market closes at www.investor.agilent.com.

About NMR

Nuclear magnetic resonance (NMR) spectroscopy is an analytical chemistry technique used in quality control and research for determining the content and purity of a sample as well as its molecular structure. It is used primarily in academia and government, the pharmaceutical, biotech and chemical industries.

About Agilent Technologies
Agilent Technologies Inc. (NYSE: A) is the world’s premier measurement company and a technology leader in chemical analysis, life sciences, diagnostics, electronics and communications. The company’s 20,600 employees serve customers in more than 100 countries. Agilent had revenues of $6.8 billion in fiscal 2013. Information about Agilent is available at www.agilent.com.

On Sept. 19, 2013, Agilent announced plans to separate into two publicly traded companies through a tax-free spinoff of its electronic measurement business. The new company is named Keysight Technologies, Inc. The separation is expected to be completed in early November 2014.

Forward-Looking Statements

This news release contains forward-looking statements as defined in the Securities Exchange Act of 1934 and is subject to the safe harbors created therein. The forward-looking statements contained herein include, but are not limited to, information regarding the separation of Agilent’s electronic measurement business; future revenues, earnings and profitability; the future demand for the company’s products and services; and customer expectations. These forward-looking statements involve risks and uncertainties that could cause Agilent’s results to differ materially from management’s current expectations. Such risks and uncertainties include, but are not limited to, unforeseen changes in the strength of our customers’ businesses; unforeseen changes in the demand for current and new products, technologies, and services; customer purchasing decisions and timing, and the risk that we are not able to realize the savings expected from integration and restructuring activities.

In addition, other risks that Agilent faces include those detailed in Agilent’s filings with the Securities and Exchange Commission, including our latest Form 10-K and Form 10-Q. Forward-looking statements are based on the beliefs and assumptions of Agilent’s management and on currently available information. Agilent undertakes no responsibility to publicly update or revise any forward-looking statement.

# # #

Contact:

Michele Drake
+1 408 345 8396
michele_drake@agilent.com

Neil Rees (U.K.)
+44 186 529 1472
neil_rees@agilent.com

Investor Contact:

Alicia Rodriguez
+1 408 345 8948
alicia_rodriguez@agilent.com

Presentations at SMASH 2014

“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

Presentation and Posters – Magnetic Resonance in Food Conference 2014 – Cesena Italy

“Liquid and Solid-State 27Al qNMR of an Elemin Senonian Trace Minerals Supplement for Identification, Chemical Structure, Quantitation of Active Ingredient in the Product, and Product Stability”, Boris Nemzer, John C. Edwards, presented at XII International Conference on the Applications of Magnetic Resonance in Food Science: Defining Food by Magnetic Resonance, Cesena, Italy, May 20-23, 2014.
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“Liquid and Solid-State Multinuclear 13C and 11B qNMR FruitexB Fructoborate Complex Nutritional Supplement. Identification, Chemical Structure, Quantitation of Active Ingredient in Product, and Product Stability”, Boris Nemzer, John C. Edwards, presented at XII International Conference on the Applications of Magnetic Resonance in Food Science: Defining Food by Magnetic Resonance, Cesena, Italy, May 20-23, 2014.
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“1H qNMR of EPA and DHA Omega-3 Fatty Acid Esters – PLS Regression Models Obtained by 60 and 300 MHz NMR – At-Line and On-Line Monitoring of a Fish Oil Nutritional Supplement Manufacturing Process”, John C. Edwards, Paul J. Giammatteo, invited oral presentation at XII International Conference on the Applications of Magnetic Resonance in Food Science: Defining Food by Magnetic Resonance, Cesena, Italy, May 20-23, 2014.

“Application of High Field and Cryogen-Free Bench-Top NMR Platforms to the Monitoring and Quantitation of PDE5 Inhibitor Adulteration of Male Sexual Enhancement Supplements”, John C. Edwards, Paul J. Giammatteo, Kristie Adams, Anton Bzhelyansky , presented at XII International Conference on the Applications of Magnetic Resonance in Food Science: Defining Food by Magnetic Resonance, Cesena, Italy, May 20-23, 2014.
Get PDF Here

Presentation and Posters at PANIC 2014

“NMR Based Authentication of Nutraceuticals, Herbal Supplements, and Food Additives: Economic- and Efficacy-Driven Adulteration of Aloe Vera, Herbal Erectile Dysfunction Supplements, and Acacia Gum”, John C. Edwards, invited presentation at the 2nd PANIC, Charlotte, NC, February 3-5, 2014.
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“Development of an Automated Complex Mixture Analysis qNMR Method within Mestrelab MNova – Application to Aloe Vera and the Beer Brewing Process”, John C. Edwards, Adam J. Dicaprio, Michael A. Bernstein, presented at the 2nd PANIC, Charlotte, NC, February 3-5, 2014.
Get PDF Here

“Small Molecule Chemistry of Spontaneously Fermented Coolship Ales”, Adam J. Dicaprio, John C. Edwards, presented at the 2nd PANIC, Charlotte, NC, February 3-5, 2014.
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“Liquid and Solid-State 1H, 13C, and 11B qNMR Analysis of Fruitex-B®– A Calcium Fructoborate Comple: Chemical Structure and identification, quantitative analysis and stability study”, Boris Nemzer, John C. Edwards, presented at the 2nd PANIC, Charlotte, NC, February 3-5, 2014.
Get PDF Here

John Edwards to be Guest Editor of 2 Special Issues of Magnetic Resonance in Chemistry Dedicated to Benchtop NMR

I have been invited to be a guest editor for Wiley publishing to pull together 2 special issues of Magnetic Resonance in Chemistry. I am putting out a general “call for papers” but I will harass people personally. We are looking for 10-20 papers for each issue.

The deadline for submission of the papers is June 30 so no-one has an excuse that there isn’t enough time. I do ask that you email me at the contact below to let me know that you are thinking of submitting and a title would be nice also (though I won’t hold you to it). We hope to have the review and revide papers (if necessary) by late October and then publish by December 2014.

The first will be on high resolution benchtop NMR in which I would like to include all permanent magnet systems capable of obtaining a spectrum. This is an open invitation to all the vendors and their customers of (in no particular order) Anasazi, Nanalysis, One Resonance Sensors, Magritek/ACT, Aspect, Qualion, Picospin, Resonance Systems, Oxford Instruments, Bruker, home built devices, I would also make the exception that HTS systems be included as they are also cryogen free.

Any papers on spectrometers, magnets, educational, industrial, academic applications, chemometrics, automated approaches, reaction monitoring, online/at-line utilization, 2D NMR, combined spectral/relaxation applications.

The second will be on low resolution benchtop NMR but I would like to exclude applications that have been around for decades (H content, SFC, oil content, spin finish). I would like to encourage new applications to be submitted and they should include hardware, magnets, spectrometers, probes, 1D/2D Laplace inversion (I’d love a review/overview of that software aspect), applications. Again – all vendors and all users of commercial and home grown benchtop TD-NMR systems please submit.

We’re looking for articles on FPGA spectrometers, software approaches (1D/2D Laplace, chemometrics), magnet design and construction, dedicated rheology analysis instruments, field cycling NMR, unilateral NMR, core analyzers, applications of all whether educational, academic, industrial.

The types of articles can be Reviews, Mini-Reviews, Tutorial, Historical, Spotlight, Perspective, Communication, Article, Application Note, Case Report, Spectral Assignments, Correspondence.

Here is the official word on the use of color (note you can have all the color figures you wish in the online version but the print version is restricted): two colour illustrations per submission are allowed free of charge, however further colour illustrations are allowed at the Editors discretion and where they are justified. Authors can have as much colour as they like in the online version as the restrictions are just for the print version.

Please contact me directly if you would like to make a submission of your work to either of the two issues: john@process-nmr.com

I have posted the authors instructions for special Issues that I was given on my website at:
http://www.process-nmr.com/pdfs/MRC_Submission_instrux.pdf

The MRC author guidelines can be found at:
http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291097-458Xa/homepage/ForAuthors.html

Herbal Supplement for Erectile Dysfunction Found to Contain Thio Structural Analog of Sildenafil (Viagra)

A herbal supplement marketed to alleviate erectile dysfunction was recently submitted for testing in our laboratory because it was surprisingly effective considering it should only contain the traditional herbals utilized for this problem such as Oyster, 2-Deoxy-D Glucose, Barberry, Snow Lotus, Bombyx Mori L., Ginger Root, Salfron Crocus.

Above: 1H NMR of ED Herbal Supplement – this is an extract of the powder from  the capsules into 80:20 CD3CN:D2O – Observed suspicious specific small molecule peaks – herbals are usually broad featureless complex mixture spectra. This is something in different – a specific drug material appears to have been added.Comparison with the spectrum of Viagra (Sildenafil Citrate) below shows a strong similarity between the 2 active ingredients.

We also obtained the COSY, 13C and DEPT NMR Spectra on the ED herbal supplement. These are shown below.

The analysis of the NMR data led us to find that the extractable components of the sample contained predominantly Sulfoaildenafil (thioaildenafil) which is a strutural analog of Sildenafil (Viagra) and is not approved by any health regulation agency for use in erectile dysfunction medicines or supplements. Apparently these structural analogs to Viagra are found widely in herbal supplements sold for this malady. I guess we have one more for the list that the FDA keeps on such dangerously adulterated products.

Solid-State 13C NMR of Drug API and Tablets

We have an excellent solid-state Doty Scientific Supersonic 7mm CP-MAS probe for our Varian UP-200 spectrometer. This is a nice field strength for solid-state 13C analyses as it allows for spectra at higher sensitivity than a 100 MHz but still has the advantage that 7 kHz is enough to push the aromatic MAS sidebands beyond 0 ppm so that more accurate aromaticity values can be calculated. The probe is still working after 20 years and we are using the original rotors and have never had to replace any of the capacitors. We have run approaching 20,000 experiments with this probe. Here are some of the nice spectra we have been getting recently on drug API and tablets.

Above: Solid-State 13C NMR of Rapamycin API

Above: Solid-State 13C NMR of Ranitidine HCl – Zantac Tablet

Above: Solid-State 13C NMR of Simvastatin 20 mg Tablet

Solid-State 13C NMR of Tylenol 3 – Acetamenaphin + Codeine