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

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.