Metabolic profiling of mouse cerebrospinal fluid by sheathless CE-MS |
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Authors: | Rawi Ramautar Reinald Shyti Bart Schoenmaker Lotte de Groote Rico J E Derks Michel D Ferrari Arn M J M van den Maagdenberg André M Deelder Oleg A Mayboroda |
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Institution: | 1. Biomolecular Mass Spectrometry Unit, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands 2. Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands 3. Department of Neurology, Leiden University Medical Center, 9600, 2300 RC, Leiden, The Netherlands
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Abstract: | The need for sensitive analytical technologies applicable to metabolic profiling of volume-restricted biological samples is high. Here, we demonstrate feasibility of capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (MS) with sheathless nano-electrospray interface for non-targeted profiling of ionogenic metabolites in body fluids of experimental animals. A representative mixture of the metabolites and body fluids of mice such as cerebrospinal fluid (CSF), urine and plasma were used as examples of low-volume biological samples for method evaluation. An injection volume of only 9?nL resulted in limits of detection between 0.7 and 12?nM for the metabolite mixture. The method allowed the detection of ~350 molecular features in mouse CSF (an injection volume of ca. 45?nL), while ~400 features were observed in mouse plasma and ~3,500 features in mouse urine (an injection volume of ca. 9?nL). The low-volume body fluid samples were analyzed directly after only 1:1 dilution with water, thereby fully retaining sample integrity, which is of crucial importance for non-targeted metabolic profiling. As little is known about the metabolic composition of mouse CSF, we identified a fraction of the molecular features in mouse CSF using accurate mass information, migration times, MS/MS data, and comparison with authentic standards. We conclude that sheathless CE-MS can be used for sensitive metabolic profiling of volume-restricted biological samples. |
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