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Quantitative high-throughput analysis of drugs in biological matrices by mass spectrometry

✍ Scribed by Gérard Hopfgartner; Emmanuel Bourgogne

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
261 KB
Volume
22
Category
Article
ISSN
0277-7037

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✦ Synopsis

Abstract

|   I. | Introduction | 195 |
|  II. | Automated Sample Preparation | 197 |
| | A.  Sample Collection | 197 |
| | B.  Sample Pooling | 197 |
| | C.  Off‐Line Sample Preparation | 199 |
| | D.  On‐Line Sample Preparation | 200 |
| |     1.  Drirect Plasma Injection | 201 |
| |      a.  Turbulent flow and large‐particle high‐flow separation | 202 |
| |      b.  Restricted‐access media columns | 203 |
| |     2.  Sample Pre‐Treatment | 203 |
| III. | Sample Analysis | 203 |
| | A.  Separation Techniques | 203 |
| | B.  Serial Approaches | 204 |
| |     1.  Fast Chromatography | 204 |
| |     2.  Monolithic HPLC Columns | 204 |
| |     3.  Packed Column Supercritical Fluid Chromatography | 205 |
| | C.  Parallel Approaches | 205 |
|  IV. | Detection | 207 |
| | A.  Mass Analyzer | 207 |
| | B.  Matrix Suppression | 208 |
| | C.  Metabolite Interferences | 209 |
|   V. | Future Perspectives and Conclusions | 209 |
| 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

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