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Review of in situ derivatization techniques for enhanced bioanalysis using liquid chromatography with mass spectrometry
Abstract
Accurate and specific analysis of target molecules in complex biological matrices remains a significant challenge, especially when ultra‐trace detection limits are required. Liquid chromatography with mass spectrometry is often the method of choice for bioanalysis. Conventional sample preparation and clean‐up methods prior to the analysis of biological fluids such as liquid–liquid extraction, solid‐phase extraction, or protein precipitation are time‐consuming, tedious, and can negatively affect target recovery and detection sensitivity. An alternative or complementary strategy is the use of an off‐line or on‐line in situ derivatization technique. In situ derivatization can be incorporated to directly derivatize target analytes in their native biological matrices, without any prior sample clean‐up methods, to substitute or even enhance the extraction and preconcentration efficiency of these traditional sample preparation methods. Designed appropriately, it can reduce the number of sample preparation steps necessary prior to analysis. Moreover, in situ derivatization can be used to enhance the performance of the developed liquid chromatography with mass spectrometry‐based bioanalysis methods regarding stability, chromatographic separation, selectivity, and ionization efficiency. This review presents an overview of the commonly used in situ derivatization techniques coupled to liquid chromatography with mass spectrometry‐based bioanalysis to guide and to stimulate future research.
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“A largely used strategy for the detection of small molecules that are not readily detected by LC-MS is “chemical labelling” (Fig. 3D).95–97”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [97]
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“Derivatization protocols have been developed for functional groups including, but not limited to alcohols, phenols, ketones, aldehydes and carboxylic acids.96,97”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [97]
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Metadata
- Authors
- Baghdady, Y. Z., & Schug, K. A.
- Affiliations
- The University of Texas at Arlington (US)
- Corresponding author
- Schug, Kevin A.
- ORCID
- Schug, Kevin A.
- Venue
- Journal of Separation Science
- Publisher
- Wiley
- Published
- 2015-11-19
- Volume
- 39
- Issue
- 1
- Pages
- 102-114
- ISSN
- 1615-9306 (ISSN-L)
- 1615-9314
- OpenAlex
- W2195492704
- Cited by
- 54
- References
- 66
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 6
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Separation Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Chemistry and Chromatography
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- in situ derivatization, bioanalysis, liquid chromatography-mass spectrometry, sample preparation, biological matrices, on-line derivatization, preconcentration, ionization efficiency, ultra-trace detection, biological fluids
- MeSH terms
- Animals, Biological Assay, Chromatography, Liquid, Humans, Mass Spectrometry
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