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Back to Reality #1- LC/MS vs. NMR

June 9, 2011
by Ryan Sasaki, NMR Product Manager, ACD/Labs

Reality #1:

LC/MS has become the primary analytical check for the medicinal chemist. I Love NMR, but it’s the reality

So how did we get here? Clearly there a lot of reasons, but one of my hypotheses is based on the evolution of open access and the walk-up environment. No doubt that moving away from the traditional analytical service departments has been a great thing from a productivity standpoint.

LC-MS lends itself really well to the open access environment. There are good systems out there that can auto-process data well and provide a nice report that gives the chemist a simple answer. In most cases, the chemists can get the answer they are looking for with a quick glance at the report. In addition, for this kind of routine analysis, the interpretation of the results is very easy.

Contrast that to NMR. How often are the printouts from the instrument good enough? Not nearly as often. More and more it is becoming common practice for the chemist to import their raw or processed data into the processing software on the instrument or in some offline processing software. Within these applications, they can get a better look at their data, zoom in on areas of interest, re-integrate the spectrum so it makes sense, perhaps even generate a multiplet report for a potential patent down the road.

Add up those tasks alone, and the chemists may be forced to spend 5-10 more minutes on a routine NMR than an LC-MS when you factor in interpretation as well! Unfortunately, the NMR instrument is not printing out an answer, it is printing out a spectrum that needs to be interpreted by the chemists which on a routine basis is a lot more difficult and complex task than checking an LC-MS for reaction completion. Furthermore, let’s keep in mind that intrepreting analytical data is not the medicinal chemists job. They are evaluated, compensated, etc. for making molecules. The more molecules the better so the inherent risk here is obvious and I don’t think it’s fair to simply “blame the chemists”

Given the above, is there any wonder why LC-MS has become the primary analytical check?

3 Replies to “Back to Reality #1- LC/MS vs. NMR”

  1. Perhaps the answer for this is much more simple…
    Have you compared the prices for both the aquisition and the maintenance of an NMR spectrometer and an HPLC/MS? This is much in favour for the LC/MS system, you can buy and care for several nice systems for the price of one NMR spectrometer…
    Have you compared the laboratory requirements in terms of space needed, floor stability etc.? You can put several LC/MS systems on the lab space needed for a NMR spectrometer, and you can put them on the top floor of an old building… 😉
    You don’t need to dedicate a whole lab to the instrument.
    And so on… 😉
    Best, Timo

  2. Hi Timo,
    Thanks very much for your comments, they are very well received. I definitely agree,and I was going to bring this up later when I discussed reality #3 in more detail. The cost is a major factor from purchase, to implementation, to maintenance,to support, etc.
    A few years back Anthony Macherone spoke at our user meeting at the ENC Conference and made this very point. Link can be found here, and specific reference is in slide 5:
    I guess the big question is whether this cost is worth the benefits of having better QC and higher library quality. It’s a really difficult question to ask and I suspect this is one of the reasons why we aren’t seeing more emphasis on NMR. A lot of companies don’t have a great handle on the number of incorrect compounds in their library nor the risks/costs associated with having misrepresented compounds.

  3. In my view, the most important factor in LC/MS vs. NMR is the amount of sample needed and the purity requirement for obtaining a meaning result.


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