1H NMR characterization of normal human cerebrospinal fluid and the detection of methylmalonic acid in a vitamin B12 deficient patient.

1H NMR was used to analyze human cerebrospinal fluid (CSF) from a group of neurological disease controls and from a vitamin B12 deficient patient. The spectra were acquired at either 7.06 or 9.40 T at ambient temperature with CSF freeze dried and reconstituted in 2H2O. 3-Trimethylsilyl propionate was used as an internal chemical shift and concentration reference. All of the CSF samples showed peaks for lactate, L-alanine, acetate, glutamine, citrate, creatine/creatinine and sugar resonances. There was good agreement between the metabolite concentrations as determined by NMR with those obtained using conventional chemical methods. 1D and 2D 1H NMR techniques along with J-coupling and T1 analysis were used to confirm the peak assignments. Methylmalonic acid could be detected and quantitated (ca 150 microM) in the CSF from the vitamin B12 deficient patient.