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Utility of Mass Spectrometry for Pharmaceutical Profiling Applications

[ Vol. 7 , Issue. 5 ]

Author(s):

Edward H. Kerns and Li Di   Pages 457 - 466 ( 10 )

Abstract:


MS has great utility for pharmaceutical profiling, the measurement of physicochemical and metabolic proper-ties that are crucial to the discovery and development of new drug candidates. An evaluation of the capabilities of MS toimprove the speed, specificity, sensitivity and cost per compound of method in development indicates when MS technolo-gies have utility compared to other analytical techniques. MS has been used successfully for methods that profile the criti-cal properties: permeability, lipophilicity, plasma and solution stability, solubility, plasma protein binding and integrity. Ingeneral, MS has utility in these methods using analytical strategies involving unique MS technologies (e.g., parallel mul-tiplexed 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 additionto quantitative and facile integration with HPLC autosamplers and other hardware that allow enhanced on-line experi-ments. Ultimately, it is important to evaluate the appropriateness of any technique that is being considered for use in amethod, to insure that it best meets all of the criteria for the organizations needs.

Keywords:

Pharmaceutical profiling, mass spectrometry, drug discovery, ADME, structure-property relationships

Affiliation:

Wyeth Research, CN8000,Princeton, NJ 08543-8000, USA.



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