Simultaneous fast HPLC-MS/MS analysis of drug candidates and hydroxyl metabolites in plasma

  • Hsieh Y
  • Brisson J
  • Wang G
 et al. 
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Abstract

A rapid bioanalytical method was evaluated for the simultaneous determination of drug discovery compounds and their potential metabolites in plasma samples within 1 min run time by fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The fast HPLC-MS/MS system is achieved by using mini-column HPLC coupled to tandem mass spectrometer which is advantageous over regular HPLC-MS/MS systems, such as a shorter chromatographic region of ionization suppression, less solvent consumption and higher throughput. Matrix ionization suppression effect of the test compounds in plasma samples when using fast HPLC-MS/MS method was examined by a post-column infusion technique. In the described example, the proposed approach has been successfully employed to determine the plasma concentration of the test compound and its hydroxyl metabolite (M+16) in monkey in the low ng/ml region. The monkey pharmacokinetic results obtained by the proposed fast HPLC-MS/MS method were in good agreement within 20% error with those obtained by the regular HPLC-MS/MS method based on the same sample preparation procedure. © 2003 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Ballistic gradient separation
  • Drug discovery compounds
  • Fast HPLC-MS/MS
  • Hydroxyl metabolites
  • Matrix ionization suppression
  • Pharmacokinetics

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Authors

  • Yunsheng Hsieh

  • Jean Marc Brisson

  • Ganfeng Wang

  • Kwokei Ng

  • Walter A. Korfmacher

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