1 H NMR characterization of normal human cerebrospinal fluid and the detection of methylmalonic acid in a vitamin B 12 deficient patient

1 H NMR was used to analyze human cerebrospinal fluid (CSF) from a group of neurological disease controls and from a vitamin B 12 deficient patient. The spectra were acquired at either 7.06 or 9.40 T at ambient temperature with CSF freeze dried and reconstituted in 2 H 2 O. 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 1 H NMR techniques along with J ‐coupling and T 1 analysis were used to confirm the peak assignments. Methylmalonic acid could be detected and quantitated (ca 150 μM) in the CSF from the vitamin B 12 deficient patient.