Assay for N τ-methylimidazoleacetic acid, a major metabolite of histamine, in urine and plasma using capillary column gas chromatography-negative ion mass spectrometry

Abstract

A gas chromatographic-mass spectrometric assay has been developed for the measurement of N τ-methylimidazoleacetic acid in urine and plasma. The method uses the isopropyl ester 3,5-bistrifluoromethylbenzoyl derivative of N τ-methylimidazoleacetic acid and electron capture negative ion chemical ionisation mass spectrometry. The derivative has very good chromatographic properties and a negative ion mass spectrum which contains only a molecular ion at m/z 422. When this ion is specifically monitored, an amount of derivative equivalent to 1 pg of parent compound can be detected. A deuterated analogue of N τ-methylimidazoleacetic acid was synthesised for use as an internal standard and this allowed the development of an assay for N τ-methylimidazoleacetic acid, in urine with a precision of 2.9% and in plasma with a precision of 1.5%.