- The use of short columns with high column flow rates and preferably with a temperature programmable injector which lowers the elution temperatures from the injector liner to the column and from the column itself (slower temperature programming rate and thinner films also help) and;
- The use of a fly-through ion source in combination with sample compounds in supersonic molecular beams (Cold EI) eliminates any ion source peak tailing and/or sample degradation on the hot metallic ion source surfaces.
The use of GC-MS with Cold EI opens the door for significantly increased range of compounds and applications that are amenable for GC-MS analysis. Consequently, GC-MS with Cold EI bridges the gap with LC-MS, helps to analyze the bottleneck hard to analyze compounds in current methods and opens the door for new and untapped opportunities in GC-MS analysis.
In Figure 4 we demonstrate the analysis of a large polar drug such as Reserpine which is unique to the 5975-SMB GC-MS with Cold EI and can not be analyzed by any other standard GC-MS. Reserpine exhibited its true molecular ion with m/z=608.3, was easily identified by the NIST library and its elemental formula (C33H40N2O9) was confirmed with the TAMI software. The small peaks near the Reserpine elution time are of its impurities including of deserpidine that eluted at 11.23 min.
|Figure 4. The analysis of Reserpine with the 5975-SMB GC-MS with Cold EI. 5 m 0.25 mm ID column was used with 16 ml/min helium column flow rate. Note the dominant true molecular ion with m/z=608.3.|
|Figure 5. The analysis of triacetonetriperoxide (TATP) using the 5975-SMB GC-MS with Cold EI. Note the low elution temperature of 69ºC. The injector temperature was 140ºC for this analysis.|
While for thermally labile and low volatility compounds the extension of the range of compounds amenable for analysis can be the difference between "can be analyzed" and "can not be analyzed" as shown above, often the analysis limits of standard GC-MS are more gradual as its response simply declines with mass and volatility due to ion source peak tailing and loss of molecular ions mass spectral peaks. The topic of intra-ion-source peak tailing is discussed in another post in this blog.
Discussion – Extending the Range of Compounds amenable for GC-MS Analysis
- Significantly extended range of thermally labile compounds that are amenable for analysis. The significantly lower elution temperatures from the GC column in combination with the use of temperature programmable injector with high injection flow rates enable a major increase in the range of thermally labile compounds that can be analyzed which is complemented and supplemented by the Cold EI enhanced molecular ions that proves the elution of intact thermally labile sample compound. In fact, GC-MS with Cold EI is equivalent and even superior to LC-MS with APCI or APPI in its range of thermally labile compounds that are amenable for analysis. In APCI and/or APPI the sample is thermally vaporized at a very hot liner like vaporization oven (400-500ºC) where the sample stays for a short time, while in GC-MS with Cold EI the sample is vaporized at much lower injector temperatures and spends much longer time at the column at much lower temperatures. Since the effect of thermal degradation exponentially depends on the temperature, Cold EI can be gentler to thermally labile compounds than APCI/APPI.
- Significantly extended range of low volatility compounds that are amenable for analysis. The significantly lower elution temperatures from the GC column with high short column flow rates enable a major increase in the range of low volatility compounds that can be analyzed. We found that we can approximately double the molecular weight and size limit of compounds that can be analyzed in comparison with standard GC-MS to about 1200 amu for non polar compounds and 800 amu for polar compounds. In fact, GC-MS with Cold EI is equivalent in its range of compounds to LC-MS with APCI or APPI.
- Significantly extended range of polar compounds that are amenable for analysis. The elimination of ion source tailing and degradation on its metallic surfaces enables the analysis of many polar compounds without their derivatization. One example given in another post in this blog is the analysis of free fatty acids in ant heads and another example is the analysis of free fatty acids in anti-foam liquid
- Significantly improved analysis of compounds that are difficult to analyze by standard GC-MS. Many compounds belong to the group of compounds that can be analyzed by standard GC-MS but their TIC signal to noise ratio is much poorer than of easy to analyze compounds and their molecular ions are weak or absent. Example of such compounds is the group nonoxinols that is shown in Figure 7. GC-MS with Cold EI significantly improves the analysis of these compounds via the elimination of intra ion source partial degradation and peak tailing plus via the provision of abundant molecular ions.
|Figure 8. A cartoon that demonstrates our perception of the average sensitivity gain of Cold EI with the 5975-SMB GC-MS with Cold EI versus sample mass, which at some point is transformed into extended range of compounds amenable for analysis.|