Advances in Mass Spectrometry, Volume 16: Plenary and by Gareth A.G. Brenton, John Monaghan, Alison Ashcroft

By Gareth A.G. Brenton, John Monaghan, Alison Ashcroft

This quantity comprises contributions in response to some of the Invited Lectures given on the sixteenth triennial foreign Mass Spectrometry convention (IMSC) in Edinburgh (September 2003) whereas the accompanying CD comprises the Abstracts of all of the accredited papers-Oral and Posters. characteristically the IMSC has a robust emphasis at the basics and new instrumentation of mass spectrometry and on instrumental advancements, and this custom has persevered. there has been, even if, an both powerful emphasis in Edinburgh on key software parts in mass spectrometry like genomics, proteomics, metabonomics; drug metabolism and bioanalysis, discovery pharma, research in pharmaceutical improvement strategies; environmental chemistry, foodstuff and meals, forensics, and engineering materials.The Invited teachers are all foreign specialists. Their articles not just summarise the present country of mass spectrometry of their personal parts of craftsmanship but in addition spotlight the present sizzling subject matters in mass spectrometry. vital for all libraries as an updated precis. - provides a present precis of mass spectrometry. - Covers either major mass spectrometric functions and advancements. - overseas staff of members.

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Extra info for Advances in Mass Spectrometry, Volume 16: Plenary and Keynote Lectures of the 16th International Mass Sepctrometry Conference

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Not surprisingly, the need to contain such escalating costs, through realization of improved efficiencies in drug discovery and decreased attrition rates in drug development, has become a major driver in today’s pharmaceutical R&D environment. In considering possible reasons for what some claim to be a decline of innovation in an industry with an enviable record of scientific achievement, it has been argued that the “easy” drug targets already are addressed by therapeutic agents which are both safe and effective, such that the industry is now faced with developing treatments for much more complex disease states with multiple causes [6], such as Alzheimer’s disease, asthma, diabetes, cancer and obesity.

Experimental details are provided in [18] Compd. ’ † Parallel experiments suggested that irreversible binding of radioactivity to microsomal protein at time zero and in the absence of an NADPH regenerating system was < 5 pmol equiv/mg protein/1-h incubation in all cases. 3 Metabolic activation of aryloxy-substituted leads in a drug discovery program. 1) detected in rat liver microsomal incubations conducted in the presence of GSH. Relevant fragment assignments rationalizing the phenyl ring as the site of metabolic activation are also depicted.

5 Metabolic activation of a pyrazinone-containing thrombin inhibitor. LC-MS/MS analysis on a linear ion trap A further example of the rich metabolic chemistry associated with 6-membered heterocycles, and of the power of LC-MS/MS combined with high-field NMR techniques, was encountered in studies of a series of inhibitors of the enzyme thrombin, a key element in the blood coagulation cascade. The structural series of interest contained a pyrazinone ring system as the central core (Fig. 5), and metabolism studies were performed early in the course of preclinical evaluation both to identify metabolic “soft spots” in the lead compounds, and to screen for possible reactive metabolite formation.

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