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Deep Proteome Profiling by Isobaric Labeling, Extensive Liquid Chromatography, Mass Spectrometry, and Software-assisted Quantification
Published on: November 15, 2017
Recent advances in high-throughput quantitative bioanalysis by LC-MS/MS
Raymond Naxing Xu1, Leimin Fan, Matthew J Rieser
1Abbott Laboratories, Department of Drug Analysis, 100 Abbott Park Road, Abbott Park, IL 60064-6126, USA. raymond.xu@abbott.com
Journal of Pharmaceutical and Biomedical Analysis
|March 16, 2007
Summary
Recent advances in liquid chromatography-tandem mass spectrometry (LC-MS/MS) enhance high-throughput quantitative bioanalysis for drug development. New techniques improve speed, resolution, and sensitivity in analyzing drugs and metabolites in biological samples.
Area of Science:
- Analytical Chemistry
- Pharmaceutical Sciences
- Biotechnology
Background:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is crucial for pharmacokinetic and metabolism studies in drug development.
- High-throughput quantitative bioanalysis of drugs and metabolites in biological matrices is essential for pharmaceutical research.
Purpose of the Study:
- To review recent advancements in sample preparation, separation, and mass spectrometry for LC-MS/MS bioanalysis.
- To highlight new techniques improving speed, resolution, and sensitivity in drug analysis.
- To discuss strategies for mitigating matrix effects in LC-MS/MS methods.
Main Methods:
- Ultra-performance liquid chromatography (UPLC) with sub-2 µm particles and monolithic chromatography for improved separation.
- Hydrophilic interaction liquid chromatography (HILIC) as a complementary technique to reversed-phase LC-MS/MS.
- 96-well plate formats for semi-automated sample preparation and on-line solid-phase extraction (SPE) with column-switching techniques.
- Various extraction sorbents for on-line SPE, including turbulent flow chromatography media, restricted access materials (RAM), and monolithic materials.
Main Results:
- New chromatographic techniques offer enhanced speed, resolution, and sensitivity compared to conventional methods.
- 96-well plate formats and on-line SPE significantly increase throughput and reduce labor.
- Emerging HILIC provides a valuable alternative for specific analytical challenges.
- Understanding and managing matrix effects are critical for accurate LC-MS/MS analysis.
Conclusions:
- Recent innovations in LC-MS/MS, including advanced chromatography and automated sample preparation, are revolutionizing drug development bioanalysis.
- These advancements enable faster, more sensitive, and more efficient quantification of drugs and metabolites.
- Effective management of matrix effects is vital for robust method development and validation in quantitative bioanalysis.
