Blog posts by Bertram

RIVM in the Netherlands uses the Spinsolve benchtop NMR spectrometer to investigate illegal drugs

June 8th, 2017, by

Dr Peter Keizers is a scientist in the Centre for Health Protection at RIVM, the Dutch National Institute for Public Health and the Environment based in Bilthoven. As a chemist, he investigates (illegal) drugs, medical devices and other medicinal products. His group studies the composition of these products and specifically look for active pharmaceutical ingredients, preferably in a quantitative way.


New Spinsolve Publications

March 19th, 2017, by

The Spinsolve is not only a perfect tool to teach NMR to Chemistry students, but its performance enables it to be used for serious research. This is evidenced in the published papers from our users. Over the last few months there has been a number of new publications featuring Spinsolve. In this post we will highlight a few of them. Click here for a full comprehensive list of publications.


Stream the Webinar: Thinking Outside the (Benchtop) Box – High-Field NMR Techniques on Benchtop Instruments

October 29th, 2016, by

Did you miss our recent webinar ? No problem, just click the red button below to stream a replay of the webinar held on 27th October 2016: Thinking Outside the (Benchtop) Box – High-Field NMR Techniques on Benchtop Instruments


Stream the Webinar Recording


In this webinar you will learn about:

  • High-field techniques that are now possible on benchtop instruments.
  • Applications and problems solved by advancements in benchtop NMR spectroscopy.
  • The size, ease-of-use, and economic advantages of benchtop instruments over high-field machines.

In recent years benchtop NMR spectrometers have become an increasingly viable alternative to high-field systems. Many demanding resolution and sensitivity requirements can now be met with modern methods and instruments. In this webinar we illustrate how a number of well-established and modern high-field NMR techniques, such as 2D, non-uniform sampling (NUS), and pure shift experiments, can be implemented on a benchtop NMR system to solve problems and applications previously considered beyond reach.

Benchtop qNMR evaluation

September 18th, 2016, by

In an earlier post on qNMR we described how benchtop NMR can be used to quantify the concentration of a sample or measure its purity. When such quantitative methods are validated, there are standard requirements for accuracy, precision, range, and linearity over that range that need to be met.

For example, the United States Pharmacopeia (USP) specifies the general requirements for a Category I NMR method when measuring a drug substance (there are other specifications for finished products and impurities). These specifications are listed in the table at the end of this post and are compared to the measured Spinsolve performance.

We have validated the Spinsolve benchtop qNMR performance by measuring the purity of one reference standard, methylsulfonylmethane (MSM), with another, maleic acid. Maleic acid is a common reference standard for qNMR, so this was used as the reference to measure the known purity of MSM (specified 99.5% pure). A spectrum of the mixture in D2O is shown in Figure 1.

Spectrum of MSM and maleic acid in D2O

Figure 1: Spectrum of MSM and maleic acid in D2O.


Quantitative benchtop NMR

September 12th, 2016, by

Quantification using any analytical method requires calibrating an instrumental response with a known reference, and then calculating the concentration of an unknown sample from the measured instrument response. One advantage of NMR compared to other analytical methods is that the signal response is linear, resulting the NMR signal intensity being proportional to the number of nuclei.

Sample concentrations and purities can be easily measured from known peaks once the proportionality constant is calibrated using a reference of known concentration and purity. Such measurement methods are known as quantitative NMR, or qNMR for short.


Gradients in NMR Spectroscopy – Part 6: Mixture Analysis by Diffusion Ordered Spectroscopy (DOSY)

July 25th, 2016, by

In part 5 we introduced the PGSE experiment to measure self-diffusion coefficients. We saw that if the peak integrals are displayed as a Stejskal-Tanner plot we can immediately identify if there is a single self-diffusion coefficient or not. This works pretty well for neat liquids, or solutions with a single type of molecule, or even polymer molecules with a size distribution. However, in real life we are often dealing with mixtures of molecules, and it would be nice if we could somehow separate the spectra of the individual compounds.

Consider for example the spectrum of a mixture of procaine and paracetamol in D2O. This is shown in the middle scan of Figure 1, along with the spectra of the pure compounds above and below. If we had only the mixture available, but not the pure compounds, it would be hard to figure out how many and which compounds are present in the mixture.

These spectra, along with all the others shown in this post, were acquired on a Spinsolve benchtop NMR spectrometer with additional hardware to enable PFGs for measuring diffusion.

Figure 1

Figure 1: Spectra of procaine (top), paracetamol (bottom), and a 1:1 mixture of both (middle) in D2O.


New Publications Page

July 22nd, 2016, by

Serving requests from our followers, we have created a list of selected peer-reviewed publications in which our Spinsolve benchtop NMR spectrometer is featured. Spinsolve is being used for research in topics such as online Reaction Monitoring, Hyperpolarisation, Ultrafast 2D NMR, Residual Dipolar Couplings and Process Control.

Please have a look at Publications.

This is a growing list, and it shows that Spinsolve is used for high-class academic research in many different fields all over the world.


Gradients in NMR Spectroscopy – Part 5: The Pulsed Gradient Spin Echo (PGSE) Experiment

July 18th, 2016, by

Part 3 discussed how a matched pair of positive/negative magnetic field gradient pulses can be used to encode spins for their displacement. Although this simple sequence has great value from an educational point of view, it is rarely used in practice due to several drawbacks.

  • The delay time between the two gradient pulses can be quite long (up to several hundreds of milliseconds or even seconds). During that time the spins acquire additional phase information due to chemical shift evolution. This will make it impossible to phase the spectrum if it contains more than one peak.
  • During the evolution the magnetisation suffers from T2* relaxation, which can lead to significant signal attenuation.
  • For this experiment to work, it is extremely important that the two gradient pulses are very well matched in length and amplitude. This is very difficult to achieve with a positive/negative pair.

In 1965, E.O. Stejskal and J.E. Tanner published a famous paper describing an experiment which avoids these issues. It is called the Pulsed Gradient Spin Echo (PGSE) experiment, and I love this experiment because it’s so simple, yet technically very challenging. It is still being used in its original form after being around for half a century. The basic idea is shown in Figure 1.

Figure 1

Figure 1: (a) Schematic diagram of the PGSE pulse sequence. (b) The phase evolution of the spins at different locations along the gradient direction. Note that the 180 degree pulse inverts the phase wrap imposed by the first gradient pulse. The second gradient pulse, which is now identical to the first one in amplitude and length, completely refocuses this phase wrap.


Gradients in NMR Spectroscopy – Part 4: A short Intermezzo on Diffusion

July 10th, 2016, by

Part 3 discussed how a matched pair of positive/negative magnetic field gradient pulses can be used to encode spins for their displacement. We can distinguish between two basic types of displacement:

  • All spins are moving together with the same speed along the same direction. This leads to a phase shift in the signal.
  • All spins are jumping randomly between positions. This results in an attenuation of the signal amplitude.

In this post we will have a closer look at this second type of movement.

It is closely related to the spreading of for example a blob of ink in a beaker filled with water, which is shown schematically in Figure 1. Initially, the blob is located within a small volume (a) near the wall, but over time it will spread out and eventually cover the entire volume (b). The Latin word for “spreading out” is “diffundere”, and therefore this process is known as diffusion.

Figure 1

Figure 1: (a) Some particles are dissolved in a beaker of water. Initially, the particles are located in a small volume near the wall. Over time, the particles randomly move around and spread evenly over the entire volume (b).

This type of random jumps was first visually observed by the Scottish botanist Robert Brown when he watched pollen grains suspended in water. Nowadays we know that diffusion (another name is Brownian motion) governs biochemical processes, and there is a great interest to measure and understand such random movements.


Epoxydized Natural Rubber Measurement

July 7th, 2016, by

When natural rubber (NR) latex is epoxydized, it is converted to a new plastic (Epoxydized Natural Rubber or ENR) with many favorable properties. Damping and anti-vibration characteristics are improved. ENR is oil resistant and has a better air impermeability i.e. better sealing properties. ENR or Epoxyprene is a speciality polymer produced from natural rubber latex, cis–1,4–polyisoprene, with epoxide groups randomly dispersed along the polymer backbone. Two grades are available commercially, Epoxyprene 25 and Epoxyprene 50, indicating 25% and 50% epoxidation respectively.

In collaboration with Kruthwong & Sprenger Co.Ltd, our main distributor for Southeast Asia, we measured the ENR concentration using the Spinsolve60 benchtop NMR spectrometer. Typical 60 MHz benchtop NMR spectra of ENR samples are shown in Figure 1. The peak at 2.7 ppm is from epoxy (E), the peak at 5 ppm is natural rubber (NR). The ENR ratio can be calculated by E/(E+NR). However, the epoxy peak at 2.7 ppm suffers from significant overlap by the tails of the CH2 resonances at 2.0 ppm. This makes the ENR measurement using standard 1D spectra inaccurate.


Figure 1: Spinsolve60 Proton NMR spectra of natural rubber samples with different ENR.

In order to obtain a clean baseline for peak integration in the region of 2.5-3.0 ppm, a T1-filter was implemented to suppress the CH2 resonances at 2.0 ppm. With this implementation, the epoxy and rubber signals can be nicely separated and integrated accurately to determine the amount of epoxy present, as shown in Figure 2.


About Bertram

Bertram works as Senior Applications Engineer for Magritek in Wellington. He gained his PhD under the supervision of Paul Callaghan and has been working in the field of NMR technology for over 20 years.