The Automation of a Commercial Fourier Transform Mass Spectrometer to Provide a Quick and Robust Method for Determining Exact Mass for the Synthetic Chemist

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Abstract
Automation of a commercially available Fourier transform ion cyclotron resonance (FTICR) mass spectrometer for the routine analysis of the synthetic products from high-speed chemistry is described. The automation includes software written by the instrument manufacturer as well as in-house-developed software that allows electronic submission of samples by the chemist and e-mailing of results back to the chemist. The use of samples of relatively high concentration (approx. 1 mg mL−1) is possible due to the protocol that has been developed, which includes dilution by the autosampler during sample injection. Though high concentrations are used for speed and convenience, the amount of sample consumed is still small at approx. 15 μg per injection. The results from this method have been shown to be both accurate (typical error range – 2.29 to 2.36 ppm, average error 1.07 ppm) and precise (standard deviation of the order of 0.3 ppm). The system is capable of analysing up to 800 samples per 24 hours. As high-speed chemistry becomes more highly utilised within Pfizer Discovery, the number of samples requiring accurate mass analysis will rise but the method we have described will prevent high-resolution mass spectrometry becoming the bottleneck in new chemical entity production. The accuracy and precision demonstrated by this method allows high confidence levels in assigned molecular formulae for expected compounds and reduces the number of possible formulae to consider when working with a compound that is not the desired product of a given reaction.