Presence and measurement of methylimidazoleacetic acids in brain and body fluids.

Abstract

N tau-Methylimidazoleacetic acid, the histamine metabolite, and its isomer, N pi-methylimidazoleacetic acid, were demonstrated and measured in rat brain and in human cerebrospinal fluid, urine, and plasma by a gas chromatographic-mass spectrometric method that is simple and specific with a detection limit of about 7 pmol (i.e. 1 ng). The acids were separated in biological samples by ion exchange chromatography, derivatized as n-butyl esters with boron trifluoride-butanol, and extracted with chloroform. Complete chemical ionization mass spectra and mass ion abundance ratios established the identity of N tau - and N pi - methylimidazoleacetic acids in the biological extracts and of imidazoleacetic acid in urine, but not in cerebrospinal fluid, plasma, and brain. The methylimidazoleacetic acids as n-butyl esters were quantified by electron impact selected ion monitoring of m/e 95 esters at different retention times. 3-Pyridylacetic acid was used as an internal standard and monitored at m/e 93. The levels of N tau-methylimidazoleacetic acid and N pi-methylimidazoleacetic acid were, respectively (picomoles/g or picomoles/ml +/- S.E.), for brain, 373, 19 +/- 13.08 and 110.33 +/- 12.44; for cerebrospinal fluid, 22.77 +/- 2.15 and 80.76 +/- 18.92; and for plasma, 84.57 +/- 13.64 and 73.64 +/- 14.50. In urine, the respective levels were 20.75 +/- 1.30 and 73.02 +/- 38.22 nmol/mg of creatinine. The origin of N pi-methylimidazoleacetic acid is not certain.