How are new drugs detected via GCMS?–mass_spectrometry

If I understand how GCMS works the results are compared to known patterns, so say a sample contains morphine then you would know this because the pattern morphine produces is known.

But what about new drugs that have never been seen “in the wild” before? Like just for an example synthetic cannabinoids:

Now assume back before it was publicly known, what would have been the result if a sample had been run through GCMS?

This part seems to indicate that it would be very unlikely that 2 different compounds would produce the same results.

To clarify further some article somewhere mentioned that before Spice was analyzed the only time that specific substance(one of the JWH- series) appeared in literature was some chemist who discovered it via synthesis.

So I was imagining say some novel drug appears and is sent to a lab for analysis. How would they classify it? Would they notice it was in a certain class of compounds and do further research?

I don’t quite get the context of your question - are you asking how a new drug would be characterised by GC-MS just in general, or is it more along the lines of how can the testers look at Usain Bolt’s urine sample and know if he’s taking something they haven’t seen before?

To answer the first part - GC-MS can’t generally be used to structurally characterise an unknown molecule on its own. It gives you a critical piece of information, the molecular weight (the MS part), plus the fragmentation pattern can be used by those skilled in the art to infer some structural information. The retention time on the column (the GC part) can also give clues as to the basic structural type - many different column types are available and have well-known interaction characteristics with different structural classes.
Beyond that, though, you would need to have access to the pure unknown compound and conduct proton and carbon NMR analysis - this is the workhorse technique for characterising unknowns. If you didn’t have the pure material, but had sufficient quantities of it in a mixture (e.g. 1g of spice) you could use preparative LC-MS to separate your drug of interest and then take it from there.

If it’s the latter question you have in mind then I don’t really know for sure. I would speculate that the high-throughput, anonymous testing regime is only going to flag up known banned substances through pattern recognition. If there was a noticeable peak on the GC-MS that the testers hadn’t seen before then you’d hope they’d try and investigate further - something like an unknown steroid would seem to be an obvious stand out as the molecular weight and polarity of steroids is within quite a narrow range (generalising a bit here).

BusyScissors: can you vary the properties of the capillary tube to get different sets of readings?

It seems vaguely similar to electrophoresis and there are certain tricks you can play there to increase the amount of information you can get from the technique.

Yes, absolutely. The capillary column can be easily changed to give you a stationary phase with different properties - say many compounds were running on top of one another you might choose another column to try and improve separation.
You can also change the type of detector that is used to give the read-outs of compounds coming off the column, with various types being available optimised for different compound classes. I don’t know if this is something that can easily be switched out though, it might be more a case of having 3 GCMS machines with different detectors installed on each.

I haven’t done much MS, but many pharmaceutical companies have GCs with both diode-array and flame-ionization detectors; whether you turn one or the other on depends on the method you are doing, but both are often possible. These instruments are modular, so generally buying one part or the other and swapping them out is doable, it’s just a matter of what you need it for.

You can change the column too, and you can also change the mobile phase; the gas that you use to push your sample through the column, as well as vary it’s flow rate, column length and even temperature. All of these things can provide better peak resolution and definition, though might have down sides also (degradation of the sample, mobile phase peaks showing up with things that elute early, etc). The same is true for liquid chromatography, with a much broader range of mobile phases possible (mixtures, changes throughout the run, polar/nonpolar ratios, organic/nonorganic ratios, etc), as well as a large variety of columns.

Identifying a completely unknown molecule is time-and-resource consuming, but it isn’t particularly hard for people who know what they are doing (I didn’t stick to working as a chemist to be particularly good at this, but some of my coworkers were amazing). MS can give you molecular weight, which right off the bat gives you a large but finite number of possibilities. Molecules break up in the MS process in fairly predictable ways, so peaks of, say, 27 are likely C2H3, while peaks at weights of 46 are likely NO2. Given the ratio of common to uncommon isotopes (and that most peaks have little adjacent ones), then unless your mystery molecule is made up completely of rare isotopes, you can rely on tables of this sort to get some idea of what fragments you have. From there you can begin to piece together a puzzle.

FTIR can give you more information: the frequencies you obtain off of that can tell you how some of your fragments are more likely to be put together, because sometimes bits adjacent to other bits move one way while setting them up differently makes them move another way. I think MS is more useful overall for identifying unknowns, but FTIR can help and is faster and cheaper to do.

NMR can tell you pretty much anything you need to know about the molecular structure of something; it can be exceedingly complex to unravel the results, but running at different frequencies or using more precise instrumentation can give you a lot of information. I never developed the skills to be very competent with NMR, though my undergrad thesis advisor was amazing at it.

Then you can look at physical properties: what does it dissolve in? What is it’s melting point, what kind of reaction does it have with chemicals used to identify known classes of drugs/molecules? All this can help you narrow down what you have. If all your testing makes something look a lot like an opioid, then odds are you have an opioid with a few modifications to it, rather than some wholly unknown structure.

Spectroscopy is a pretty cool field.