Procedure for the monitoring of gabapentin with 2,4,6-trinitrobenzene sulfonic acid derivatization followed by HPLC with ultraviolet detection.

association between the 259R allele and lower concentrations of holo-TC in plasma (8, 21). Nevertheless, holo-TC in CSF was reduced in patients with the 259PR and 259RR genotypes, showing that the polymorphism indeed affected holo-TC concentrations in CNS. Holo-TC concentrations in plasma and CSF were highly correlated, which is compatible with the notion that all holo-TC in CSF originates from plasma and needs to pass the blood–brain barrier to enter the CNS. Comparison of the slopes of the linear correlation equations for the homozygous 259RR and 259PP genotypes suggests that holo-TC encoded by the 259R allele crosses the blood–brain barrier less efficiently or is less stable in CSF than 259P-encoded holo-TC. Begley et al. (13 ) showed that human astrocytes synthesize and secrete TC. Thus, a certain proportion of total TC in CSF most likely originates from within the CNS. One is tempted to speculate that the disrupted correlation between plasma and CSF concentrations of total TC in individuals with the 259PR and 259RR genotypes may reflect up-regulation of TC synthesis within CNS in response to decreased import of B12 across the blood– brain barrier. A similar relationship between vitamin B12 and total TC was seen previously in plasma in which B12 concentrations were inversely correlated with total TC, possibly reflecting B12-mediated regulation of expression or clearance of the protein (22 ). In conclusion, the TC 259R allele is associated with lower TC concentrations, especially in CSF in patients with Alzheimer disease. We plan to repeat the study in other populations and explore the possible association between the polymorphism and neuropsychiatric symptoms attributable to vitamin B12 deficiency.