Additional Selectivity Considerations for Mass Spectral Detection

3 Additional Selectivity Considerations for Mass Spectral Detection 

Sources such as the peer-reviewed scientific literature and reference texts may provide information on mass spectral fragmentation of the compound and eliminate the need to conduct experiments to characterize and map the fragmentation pattern. However, the fragmentation results previously reported in the literature should be verified using the equipment that will be used in validation and subsequent routine implementation of the method. While the same fragments and transitions should be observed on different instruments, variations may be observed in ion ratios, particularly when there are differences in source geometry of the instruments used in the reported study and the instrument on which the new method is being developed and validated. When literature sources are used for selection of the ions to be monitored, these should be referenced in the validation report. 

Guidance on the fitness for purpose of mass spectro-metric methods from the American Society for Mass Spectrometry (ASMS) includes certain basic principles found in most documents on confirmatory analysis using mass spectrometry  

The early work on requirements for confirmatory mass spectrometric methods was undertaken to address a regulatory requirement for the analysis of carcinogens established in 1977 by the US Food and Drug Administration. A paper published in 1978 demonstrated the minimum number of peaks and the specifications for relative ion abundances for each peak required to uniquely identify diethylstilbestrol from a GC-MS spectral library containing El spectra of 

000 compounds. The same results were obtained when the work was repeated at an ASMS workshop in 1997, but this time were based on comparison with a library containing 270,000 GC-MS El spectra. The initial library search looked for any match for an ion with mh 268 and gave 9995 matches out of the 270,000 spectra in the library. Addition of a second ion, miz 239, reduced the number of matches to 5536, then requiring a relative abundance of 90-100% for mIz 268 and 10-90% for mIz 239 reduced the number of matches to 46. Reducing the range within which the relative abundance of miz 239 must fall to 50-70% led to only nine spectral matches from the library. Addition of miz 145 to the ions to be matched and specifying that the ions must display relative abundances of 90-100% for m z 268, 50-70% for miz 239, and 45-65% for miz 145 produced a match with only the spectrum for DES contained in the library of 270,000 spectra. 

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