Integrated high capacity solid phase extraction-MS/MS system for pharmaceutical profiling in drug discovery


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Journal of Pharmaceutical and Biomedical Analysis 34 (2004)1-9 Edward H. Kerns a,, Teresa Kleintop a, David Little b, Thomas Tobien c, Larry Mallis d,LiDia, Mei Hu a, Yan Hong a, Oliver J. McConnell d a Wyeth Research, CN8000, Princeton, NJ 08543-8000, USA b Micromass, Manchester, UK c LEAP Technologies, Carrboro, NC, USA d Wyeth Research, Collegeville, PA, USA Received 16 September 2002; received in revised form 20 March 2003; accepted 1May2003

Abstract A method is described for use in analysis of samples from pharmaceutical profiling of early drug discovery compounds. The method consists of a high capacity autosampler which injects samples into one of two solid phase extraction columns operated in parallel for alternating trapping, washing and elution into a tandem quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) MS/MS mode. A primary method, which is useful for 80-90% of compounds, and a secondary method, which is useful for a majority of the remaining compounds, are described. No analytical HPLC column is used and the analysis rate is approximately 50 samples/h. Specificity is obtained using MRM analysis. Application of the method for high capacity analysis of metabolic stability samples is described.

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