Mass Spectrometry

Biography

Biography: Alberto Fontana

Abstract

The need of a continuous productivity increase in the pharmaceutical industry motivated the development of new Open-Access tools on many analytical techniques [1-5]. On LC, these platforms have been commonly used with low-resolution MS detectors while they have been reported with very limited automation on high-resolution MS spectrometers [6]. Typically, samples with concentration ranges around 0.1 mg/mL are prepared by medicinal chemists for reaction monitoring and for UV purity assessment. Together with the evolution of the instrumentation, new software packages to automatically process HRMS data have appeared [7, 8]. These systems are typically run by specialists and developed for biological samples with compounds in concentrations of µg/mL range.  In this work, the development of a Fully Automated Open-Access methodology on a UHPLC-DAD/ESI-QTOF system is reported, being applied to medicinal chemistry discovery projects from Janssen R&D. With the first MS conditions applied, accuracies < ±1 mDa were not achieved in 20-30% of the cases in ESI+ due to oversaturation. After optimization of MS conditions, a new ESI+ method was implemented. This method has been used by chemists for more than 2.000 compounds from structurally diverse chemical series with a success >98% in exact mass determinations. For the other 2 % of the samples, specific conditions are used. Upon training, chemists log-in samples and interpret the results by themselves in 90-95 % of the cases. To our knowledge, this the first time that this Full Automation has been achieved for an Open-Access LC-DAD-HRMS platform developed for end-users in a pharmaceutical environment.