Simultaneous determination of histamine and N tau-methylhistamine in human plasma and urine by gas chromatography--mass spectrometry.

A new and sensitive method is described for the determination of histamine and N tau-methylhistamine in human plasma and urine by gas chromatography--mass spectrometry. 15N2-Labeled histamine and N tau-[methyl-d3]methylhistamine were used as internal standards. Histamine and N tau-methylhistamine were converted to the derivatives N alpha-heptafluorobutyryl-N tau-ethoxycarbonylhistamine and N alpha-heptafluorobutyryl-N tau-methylhistamine, respectively. After these derivatives had been purified on a small column packed with CPG-10, the molecular ions were monitored during selected ion monitoring. Linear standard curves were obtained in the range of 0.5-10 ng/ml for both compounds. The reliability of the histamine analysis was demonstrated by using two different ion pairs, while a comparison with results from two different derivatizations on the same urine sample also established the specificity of the N tau-methylhistamine analysis. An increase of 1 ng of histamine in the plasma could be precisely determined by the present method. The histamine content of plasma from five normal subjects was determined as 0.83 +/- 0.37 (S.D.) ng/ml and the N tau-methylhistamine content in most subjects was below the limits of this measurement. High excretion of histamine was noted in the urine collected in the early morning from a patient with nephritis.