Automated high resolution mass spectrometry for the synthetic chemist

Exact mass measurement at high resolution is an important tool alongside ot her spectroscopic methods to help confirm the structure of a novel compound prepared by the synthetic chemist. Exact mass measurement is used in the p harmaceutical industry to confirm the expected empirical formula of a produ ct when problems have been experienced using elemental analysis. Because of the amount of manual intervention necessary when acquiring exact mass meas urements, especially when using probe ionization techniques such as fast at om bombardment ionization or electron ionization, this method has been seen to be time consuming and labor intensive for the mass spectrometrist. An a utomated high resolution mass spectrometric method has been developed at Pf izer Central Research which has streamlined exact mass measurement. The met hod, which uses electrospray ionization on a double focusing mass spectrome ter, is described. The samples are analyzed using a flow injection techniqu e, with sodiated polyethylene glycol present in the mobile phase to provide mass reference peaks. The data are acquired and processed using a macro de veloped "in house." This automated technique can process 15-20 samples an h our including data processing and report generation, using very small amoun ts of compound (similar to 25 mu g), but more importantly it can be left to run unattended overnight. This allows the instrument to be used for more c omplex experiments during the day when it is important to have a mass spect rometrist present. The results presented here demonstrate that this method gives exact mass measurements within an acceptable Limit of 5 ppm, and the variation on one sample, injected 10 times, is not excessively high (-1.8 t o +1.6 mDa). (C) 1999 American Society for Mass Spectrometry.