Utility of mass spectrometry for pharmaceutical profiling applications.
MS has great utility for pharmaceutical profiling, the measurement of physicochemical and metabolic properties that are crucial to the discovery and development of new drug candidates. An evaluation of the capabilities of MS to improve the speed, specificity, sensitivity and cost per compound of method in development indicates when MS technologies have utility compared to other analytical techniques. MS has been used successfully for methods that profile the critical properties: permeability, lipophilicity, plasma and solution stability, solubility, plasma protein binding and integrity. In general, MS has utility in these methods using analytical strategies involving unique MS technologies (e.g., parallel multiplexed interfaces, trap-and-elute), orthogonal detection to UV, high sensitivity for low LOQs, low concentration studies, highly specific MS/MS SRM, combinatorial analysis, use of internal standards, providing initial structural data in addition to quantitative and facile integration with HPLC autosamplers and other hardware that allow enhanced on-line experiments. Ultimately, it is important to evaluate the appropriateness of any technique that is being considered for use in a method, to insure that it best meets all of the criteria for the organization's needs.
Kerns
Edward H
EH
Wyeth Research, CN8000, Princeton, NJ 08543-8000, USA. kernse@wyeth.com
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Li
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D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004058:Diffusion; D004355:Drug Stability; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015203:Reproducibility of Results; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations