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Keywords:

  • high-throughput analysis;
  • biological fluids;
  • quantitation;
  • LC–MS

Abstract

  I.Introduction195
 II.Automated Sample Preparation197
 A.  Sample Collection197
 B.  Sample Pooling197
 C.  Off-Line Sample Preparation199
 D.  On-Line Sample Preparation200
     1.  Drirect Plasma Injection201
      a.  Turbulent flow and large-particle high-flow separation202
      b.  Restricted-access media columns203
     2.  Sample Pre-Treatment203
III.Sample Analysis203
 A.  Separation Techniques203
 B.  Serial Approaches204
     1.  Fast Chromatography204
     2.  Monolithic HPLC Columns204
     3.  Packed Column Supercritical Fluid Chromatography205
 C.  Parallel Approaches205
 IV.Detection207
 A.  Mass Analyzer207
 B.  Matrix Suppression208
 C.  Metabolite Interferences209
  V.Future Perspectives and Conclusions209
Acknowledgments 210
References 210

To support pharmacokinetic and drug metabolism studies, LC–MS/MS plays more and more an essential role for the quantitation of drugs and their metabolites in biological matrices. With the new challenges encountered in drug discovery and drug development, new strategies are put in place to achieve high-throughput analysis, using serial and parallel approaches. To speed-up method development and validation, generic approaches with the direct injection of biological fluids is highly desirable. Column-switching, using various packing materials for the extraction columns, is widely applied. Improvement of mass spectrometers performance, and in particular triple quadrupoles, also strongly influences sample preparation strategies, which remain a key element in the bioanalytical process. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 22:195–214, 2003; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/mas.10050