- It has uniform compound independent response, thus detected impurity concentrations can be assessed, and those below 0.1% can be neglected
- It often provides EI-based library identification, which is usually improved by the presence of an enhanced molecular in Cold EI plus structural information from the full display of fragment ions
- Cold EI ionizes non-polar as well as polar analytes
- It does not suffer from any ion suppression effects
- Total ion mass chromatograms in Cold EI often provides greater sensitivity than ESI-LC-MS
- Cold EI has much greater range of compounds amenable for analysis than any other GC-MS.
GC-MS with Standard EI System: Agilent 7890B-5977B GC-MS with extractor ion source.
- Enhanced Molecular Ions: Cold EI provided abundant molecular ions to all the impurities as well as to Haloperidol while standard EI did not provide a molecular ion to any of the impurities. For Haloperidol itself Cold EI provides 18% molecular ion abundance while in standard EI is was 0.14% and masked by an equally abundant m/z=374 (M-1) (As shown in Figure 2). Typically, large and labile compounds (on the GC-MS scale) such as drugs and their impurities have weak or no molecular ions in standard EI MS. Thus, the feature of enhanced molecular ion in Cold EI is a must in impurities analysis since the impurities are not typically found in the library hence without having trustworthy molecular ions they can-not be identified.
- Improved Identification: The combination of enhanced molecular ions, low baseline and column bleed noise plus clear peaks resulted in far better impurities characterization. As an example shown in Figure 1, the arrow indicated impurity was identified with Cold EI by the NIST library as haloperidol – water (M-H2O, possibly via water elimination) as confirmed by the Cold EI molecular ion and fragment ions. We found molecular ions for all the observed impurities of m/z= 189, 327, 341, 355, 357, 371, 375 and 387. For example, the impurity with m/z = 371 exhibited the same fragmentation pattern as haloperidol thus it is concluded to be haloperidol minus 4 hydrogen atoms.
- Superior Chromatography: Cold EI exhibits much better chromatographic separation despite its use of a shorter column and higher column flow rate. The main reason for this is the elimination of ion source peak tailing for the polar impurities in the fly-through contact-free Cold EI ion source. The high column flow rate further increases the column sample capacity and thus reduces chromatographic peak fronting of the API.
- Superior TIC sensitivity: Cold EI exhibits over an order of magnitude better total ion mass chromatogram sensitivity. In addition, the ratio of impurities peaks to baseline noise was far better for Cold EI.
- Superior quantitation: Cold EI exhibits far better quantitation and enabled the quantitation of all the eight observed impurities while in standard EI no impurity could be quantified. The arrow indicated impurity was measured by the Agilent percent report as having 0.29% abundance.
- Faster Analysis: Cold EI resulted in three times faster analysis.