Metabolic profiling of mouse cerebrospinal fluid by sheathless CE-MS.
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.
Biomolecular Mass Spectrometry Unit, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Rawi
R
Ramautar
Reinald
R
Shyti
Bart
B
Schoenmaker
Lotte
L
de Groote
Rico J E
RJ
Derks
Michel D
MD
Ferrari
Arn M J M
AM
van den Maagdenberg
André M
AM
Deelder
Oleg A
OA
Mayboroda
D000818:Animals; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D019075:Electrophoresis, Capillary / Q000379:methods*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*