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Bioanalysis. 2012 Dec;4(23):2833-42. doi: 10.4155/bio.12.258.

Investigation of basic mobile phases with positive ESI LC-MS for metabonomics studies.

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King's College London, School of Pharmacy, Stamford St, London SE1 9NH, UK.



Accurate mass based LC-MS combined with statistical analysis is established as a core analytical technology for metabonomic studies. This is primarily due to the specificity, sensitivity and structural elucidation capabilities of the technology. The vast majority of these studies are performed using acidic-based mobile phases in combination with positive ESI mode LC-MS. Recent studies have investigated the use of highly basic pH mobile phases (>10 pH units) in bioanalytical studies that utilize positive ESI mode LC-MS. This non-traditional combination has been shown to improve analyte retention, chromatographic peak shape, and S/N for a variety of probe pharmaceutical compounds in biofluid samples.


The incorporation of basic pH mobile phases resulted in increased retention for analytes that where comparatively weakly retained by a traditional acidic-modified mobile phase. Increased resolution of isomers, which otherwise co-eluted under acidic conditions, was observed. Moreover, the implementation of basic pH mobile phases further allowed for the detection of complementary marker ions.


Basic pH mobile phases utilized with positive ESI mode LC-MS have the potential for producing increased information from metabonomic studies and could lead to the detection of analytes that may prove to be valid biomarkers.

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