My name is Matt Cheselka and I've been developing a cannabis testing lab concept using NMR Spectroscopy. I appreciated the passion and knowledge you showed during MITA's webinar 'The Future Of Lab Testing in AZ' on 9 July 2020, which is why I'm contacting you.
One of my previous jobs was as an electronics tech with a small company that serviced and repaired the analog amplifiers of NMR Spectrometers. This is when I first learned about NMR and was amazed by its capabilities. When I started looking into using NMR for testing back in 2016, I was surprised that the cannabis industry wasn't already using this amazing and mature technology.
Since 2016, I've been slowly developing a business plan and doing some experiments to convince myself that quantitative measurements of compounds in complex samples using NMR could be done. I was able to measure a number of samples of non-cannabis essential oils at my local university's (Univ of Az) 400 MHz automated Bruker system. The results from my crude sample prep (in my messy office with kitchen scales and eyedroppers!) and measurements (no instrument control whatsoever) were surprisingly accurate and precise (10's of ppm, v/v).
I know that in complex samples like cannabis there are dozens to hundreds of individual compounds. The spectra of these samples are equally complex, but no more so than astronomical spectra (which I'm also very familiar, being an astronomer). THCA, for example, has 30 hydrogen atoms. This means that there are at least 30 1H spectral peaks -- each of which can be quantified but only one is needed for an accurate measurement. Same goes for all the other compounds in the sample. An NMR spectrum shows everything in the sample with a single measurement. Given more control over the NMR instrumentation and better sample prep, I'm convinced that NMR could be at least as good as (and probably better than) LC, GC, or MS. As far as I can tell, the only thing NMR wouldn't be able to at all is heavy metal analysis. Even pathogen detection is possible.
Measuring a prepared sample using NMR is also fast (measurement and analysis takes seconds). This translates to high volume and quick turnaround, which will make the cannabis testing bottleneck quite a bit less problematic. This also means less instrumentation, which translates to less personnel required and less overall operational cost and less cost to customers. Dispensaries and growers will appreciate providing much smaller sample sizes since NMR is non-destructive to the sample, and so can be measured multiple times when necessary. There are other advantages I've realized, but I'll leave those to later discussions, if any.
There's still much to do, including: creating reference spectra for each molecule that will be measured, preparing samples using adequate lab equipment, having full control of the NMR spectrometer, creating a software package for automated analysis (I'm also a software engineer), and of course acquiring the NMR Spectrometer itself. I've determined that a 600 MHz system will provide the resolution needed for these very complex spectra.
I'd like to hear what you think about using NMR for cannabis testing. I don't have the experience, connections, or financial resources to start up a testing lab, but my analysis shows that it's viable and could be very competitive and profitable. Maybe starting something completely new isn't necessary if a lab like C4 would take it on. That's my hope. All it needs is someone to run with it, and I'd like to help as much as I can. Maybe if you're not interested, you know someone who might be.
All the best and kind regards, Matt Cheselka
I got a very nice reply three days later:
Sounds fascinating and in theory would be a game changer for labs. This would need to be validated out the wazoo and independently validated after that. Anything we do we must show our two accrediting bodies (ISO and AZDHS) that it is scientifically defensible, repeatable and as accurate as the alternate methods of testing. If you have this type of validation ready I would be happy to look through and see further what your idea entails. Thanks for the email.
Ryan
Inspired, I replied back on the 24th:
Hello Ryan,
Thank you so much for your response. I'm glad that you appreciate how much NMR could improve cannabis testing. LOL most people's eyes glaze over once I start talking about NMR. Understandable but frustrating at the same time.
NMR is the oldest and most mature of the modern analytical techniques, having been discovered by Rabi back in 1938. In 1944, Rabi was awared the Nobel Prize in Physics for this work. As far as I know, no other analytical technique has a Nobel Prize winner as an original creator. NMR Spectroscopy was first described in 1946. LOL the physicists didn't see any practical use for NMR, but the chemists saw the potential in terms of molecular discovery, structure determination, qualification, and quantification. Gaoni and Mechoulam first described the active agent in cannabis (d9-THC) using NMR Spec in 1964.
Even though NMR has been around for 80 years and modern NMR Spectroscopy is very sophisticated, experts in the field tell me that we've 'barely scratched the surface' when it comes to what can be done.
To address your specific request for NMR Spec validation, the quickest and easiest way is to throw a bunch of papers at you. I've attached a few to this email:
- the files named 'paper001.pdf' and 'paper002.pdf' describe NMR Spec validation specifically.
- 'paper003.pdf' is a doctoral dissertation by Soininen whom I've had a little correspondence with, and has been very supportive and encouraging. Section 1.4 of his paper discusses validation.
- 'paper004.pdf' by Bharti and Roy is the paper I've referred to frequently when working on this project. Section 8 covers NMR Spec validation.
- 'paper005.pdf' describes working with NMR Spec in the context of ISO 17025 and ISO guide 34.
- 'paper006.pdf', 'paper007.pdf', and 'paper008.pdf' examines using NMR Spec for pharmaceutical and natural product measurements.
- 'paper009.pdf' and 'paper010.pdf' are some of the (currently) fairly rare papers about using NMR Spec for cannabis analysis.
There are 80 years' worth of examples, but I hope this gives you a pretty good sense of the current status of NMR Spec as a valid and mature analytical tool.
Kind Regards and my apologies for the length of these emails, Matt Cheselka
No response. I waited for over two weeks (12 August) and then sent him this:
Hi Ryan --
It's been a couple of weeks and I haven't heard back from you, so I can only assume you're too busy (which I understand!) and / or my concept of using NMR for testing doesn't interest you.
Thanks so much for C4! Testing labs are so important for patients and other cannabis consumers! Hopefully you'll be able to keep up with the volume, especially when Prop 207 passes.
Sorry to have bothered you.
Kind Regards and All The Best, Matt
That last sentence was intended to be a jab.
This interaction is another very strong indication that the only one who's gonna do this is me.
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