NB-818 is expected in clinical use to produce an antihypertensive effect and simultaneously to promote an increase in cerebral blood flow, owing to its vasodilator activity. To determine NB-818 levels in human plasma for pharmacokinetic studies, a capillary column gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) method was employed. Because NB-818 was degraded under GC conditions, stable derivatives had to be prepared for GC/MS measurements. Reaction of NB-818 with silylation agents produced derivatives quantitatively. In the silylation, however, the carbomoyl group of NB-818 was replaced by silyl moieties. NB-818 is possibly metabolized at the carbamate moiety alone, giving a compound with a hydroxymethyl group in place of the carbamoyloxymethyl group. Since this compound and NB-818 gave the same derivative, efforts were devoted to separating them. A detection limit below 0.1 ng ml-1 was attained. The calibration curve was linear in the concentration range 0.1-10 ng ml-1 (r = 0.9998), and the coefficient of variation was 5.5% and 3.1% at concentrations of 1 and 10 ng ml-1, respectively.