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  • Transformations in pharmaceutical research and development, driven by innovations in multidimensional mass spectrometry-based technologies

    Type:
    Article
    Description/Abstract:
    In the pharmaceutical industry, there is a tremendous need for qualitative and quantitative analysis of target analytes such as peptides, proteins, drugs, metabolites, biomarkers, impurities, and degradation products in various mixtures including synthetic reactions, in vitro cultures, biological fluids, drug substances, finished products, and many others. To provide adequate specificity for analysis in these complex mixtures, multidimensional analytical techniques are required. Mass spectrometry plays a central role in many of these multidimensional approaches to mixture analysis because it provides an unparalleled combination of sensitivity and specificity that is useful for both molecular identification and quantitative applications. Recent innovations in mass spectrometry and industrial implementation of these advances have transformed many aspects of pharmaceutical research and development. Data that were previously unattainable, or were not collected due to exorbitant cost or time constraints, can now be obtained using mass spectrometry-based technologies. The impact of these innovations has been most dramatically felt in early stages of discovery, as more data are available to make critical decisions, such as selecting compounds for advancement to costly preclinical and clinical trials. New MS technologies have also accelerated the progression of drug candidates through development and toward regulatory approval. Here, five major categories of pharmaceutical applications of mass spectrometry are reviewed. They are new chemical entity characterization, biomacromolecule characterization, bioanalytical quantitation, metabolite identification, and impurity and degradation product identification. A brief historical perspective and evolution of technologies for each application area are presented. Those discussions are followed with a description of the current strategies for implementation of the tremendous capabilities of the state-of-the-art approaches, along with representative applications. In addition, emerging technologies for each application area are presented to indicate the future directions of instrumentation for mixture analysis in the pharmaceutical industry. (Int J Mass Spectrom 212 (2001) 135–196) © 2001 Elsevier Science B.V.
    Creator/Author:
    Harbol, Kevin L.; Greis, Kenneth D.; Hoke, Steven H.; Morand, Kenneth L.; Baker, Timothy R., and Dobson, Roy L. M.
    Submitter:
    Kenneth Greis
    Date Uploaded:
    03/03/2017
    Date Modified:
    04/07/2017
    Date Created:
    2001-11
    License:
    All rights reserved

  • Fuzzy logic control applications for second order problems with low damping

    Type:
    Article
    Description/Abstract:
    A general methodology has been developed for the design of a robust control law for a family of lightly damped second order problems. In this research effort, the passivity approach has been extended to systems having non-collocated input/output pairs by introducing an observer that incorporates the nominal dynamical model of the plant. The developed passive observer-based control law emulates numerous dynamic vibration absorbers which are tuned to a targeted frequency using classical methods and the tuning ratios are time-invariant. However, the uniqueness of this approach is that the damping parameters of the emulated absorbers are continuously varied by means of a fuzzy logic control algorithm to provide near minimum-time suppression of vibration. The developed approach is applied to both several benchmarks in the field of structural dynamics as well as experiments using piezo-ceramic sensors and actuators. Results show that this methodology provides stability and performance robustness on the one hand as well as requiring relatively low amount of actuation authority for desired nominal plant closeloop behavior.
    Creator/Author:
    Weller, Tanchum; Cohen, Kelly, and Ben-Asher, Joseph
    Submitter:
    Kelly Cohen
    Date Uploaded:
    02/03/2017
    Date Modified:
    04/05/2017
    Date Created:
    2001-11
    License:
    All rights reserved