H-1-NMR CHARACTERIZATION OF NORMAL HUMAN CEREBROSPINAL-FLUID AND THE DETECTION OF METHYLMALONIC ACID IN A VITAMIN-B12 DEFICIENT PATIENT

H-1 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 (H2O)-H-2. 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 H-1 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-mu-M) in the CSF from the vitamin B12 deficient patient.