Abstract
We applied a new technique for quantitative linear range shift using in-source collision-induced dissociation (CID) to complex biological fluids to demonstrate its utility. The technique was used in a simultaneous quantitative determination method of 5-fluorouracil (5-FU), an anticancer drug for various solid tumors, and its metabolites in human plasma by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC/ESI-MS/MS). To control adverse effects after administration of 5-FU, it is important to monitor the plasma concentration of 5-FU and its metabolites; however, no simultaneous determination method has yet been reported because of vastly different physical and chemical properties of compounds. We developed a new analytical method for simultaneously determining 5-FU and its metabolites in human plasma by LC/ESI-MS/MS coupled with the technique for quantitative linear range shift using in-source CID. Hydrophilic interaction liquid chromatography using a stationary phase with zwitterionic functional groups, phosphorylcholine, was suitable for separation of 5-FU from its nucleoside and interfering endogenous materials. The addition of glycerin into acetonitrile-rich eluent after LC separation improved the ESI-MS response of high polar analytes. Based on the validation results, linear range shifts by in-source CID is the reliable technique even with complex biological samples such as plasma.
Original language | English |
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Pages (from-to) | 1882-1886 |
Number of pages | 5 |
Journal | Biomedical Chromatography |
Volume | 30 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2016 Nov 1 |
Keywords
- 5-fluorouracil
- LC/ESI-MS/MS
- human plasma
- in-source CID
- linear range shift
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry