Residual Solvents in Cannabis – to MS or not to MS?

Over the past few months, I’ve gotten numerous questions about the best detection method for terpenes and residual solvents in cannabis. It seems that a lot of people are purchasing GC-MS instruments for both of these analyses. While GC-MS is indeed a powerful tool, it’s not really necessary for either analysis. In fact, the use of MS for residual solvent analysis can be problematic enough to make its use prohibitive. So what’s the best analysis and detection method for both terpenes and residual solvents? The humble GC-FID. If you’re interested in the reasons why, read on! I’ll be splitting this blog into two parts (residual solvents and terpenes), so make sure to stay tuned for the next portion on terpenes to be posted in a few days.

When most people think about doing trace analyses, their first thought is to go with the most sensitive piece of equipment they can easily get their hands on, which is MS, which can be operated in selected ion monitoring mode. Most of the time, this is a really good approach, but for residual solvents – especially cannabis residual solvents – this can backfire on you due to the air that is injected along with your headspace sample. Remember headspace sampling involves injection of a large volume of gas from your headspace vial. This is completely different from a liquid injection in which a very small amount of liquid is injected and no air is introduced into the system.

Let’s pretend that we have a sample of headspace containing 500ppm of butane. That’s a lot of butane, but if we think about it another way, our sample contains 99.95% room air. Since butane often elutes under the tail end of our air peak, when butane elutes from our column, it’s also eluting with a much larger amount of air. When both butane and air are introduced into a mass spectrometer, the much larger amount of air will interfere with butane in the MS source. This interference may cause signal suppression, resulting in loss of sensitivity and linearity.

In addition to direct interference of air for butane, most of the rest of our analytes (through pentane) all share very small mass fragments. One of the drawbacks for MS is that in general, MS has low detectability for low molecular weight fragments due to background interferences from leaks, column phase, and carrier gas impurities. So most of the sensitivity you gain by purchasing a MS is lost due to interferences. In reality, FID is generally at least as sensitive as MS for analysis of low molecular weight volatiles, if not more, and FIDs are blind to air, which is important with headspace analyses of early-eluting compounds.

Remember to stay tuned for part two of this blog, which will discuss terpene analysis via GC-MS versus GC-FID!

2 Responses to “Residual Solvents in Cannabis – to MS or not to MS?”

  1. Jason Patricio says:

    Aloha, I wanted to know if you might could help me with a question concerning SRI 8106C GC-FID instrumentation. I wanted to know when using this instrument in the analysis of cannabinoid and terpenoid potency and residual solvent analysis, what is the best method for validating the instrumentation for proper accuracy in results; validating the external standards; and validating the results and methodology. I am a molecular scientist and botanical pharmacologist and I have been gaining interest in the proper testing of Cannabis phyto-compounds and residuals, unfortunately for as much knowledge that I have, I feel that there are more topics I may still need to comprehend. Any shared knowledge or suggestions of where I might can investigate my inquiries more is much appreciated. Mahalo (thank you) in advance for your kokua (help).

  2. Hi Jason,

    Thank you for commenting! While validation methods vary somewhat between industries, they all consist of sets of experiments to ensure that your method performs adequately. Most validations include: precision, accuracy, LOD/LOQ, linearity, recovery, robustness, and sample stability. There are other validation experiments that can be performed, but the ones I listed are the most common. Below are a couple of documents that I feel do a good job of explaining each part of a validation. The first document is more general and gives short descriptions of each validation step, while the second document goes into detail regarding requirements for the different steps of the validation:
    Reviewer Guidance: Validation of Chromatographic Methods
    Guidance for Industry: Bioanalytical Method Validation
    I’m not suggesting that you follow these guidance documents exactly – especially the second one, which includes some very stringent testing, but hopefully they will give you an idea of the parts of a validation study. If you’re validating to obtain a certification or accreditation, then be sure to check with the certifying/accrediting body before starting your validation to make sure what you plan to do covers their requirements. If you’re validating simply because it’s good science, then I heartily congratulate you, and I would buy you the Hawaiian drink of your choice if I could.

    If you need to get into more detail with this, please feel free to contact me directly (

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