Differential diagnosis of histamine intolerance syndrome

A method of diagnosis of histamine intolerance syndrome in a subject suspected of suffering from insufficient secreted DAO activity and/or deficient HNMT activity, comprising the steps of:

• obtaining a sample of plasma or serum from said subject suspected of suffering from histamine intolerance;
• adding to said sample a predefined amount of stable isotope-labelled histamine to produce a defined concentration of isotopically labelled histamine in said sample, wherein the stable isotopic labelled histamine is selected from histamine 15N-labelled at positions at anyone or more nitrogen position or a histamine 13C-labelled at anyone or more carbon positions or a histamine deuterium labelled at anyone or more hydrogen position, or a histamine containing a combination of stable isotope labels;
• incubation of said sample for a predefined period under physiological conditions to obtain inactivation of said isotopically labelled substrate by the activity of DAO and/or enzyme contained in said sample of plasma or serum;
• adding an aqueous buffer containing stable isotope labelled internal standards;
• adding an aprotic solvent miscible with the aqueous sample to the samples, or a predetermined aliquot thereof, and removing proteins and organic salts from the samples;
• determining the amounts of isotopically labelled histamine in said sample and one or more other isotopically labelled inactivation products of histamine using hydrophilic interaction chromatography and mass spectrometry which comprises an LC-MS/MS technique;
• and
• calculating the histamine inactivation activity and/or histamine inactivation activity and/or the DAO activity in plasma or serum of the subject on basis of the amounts of isotopically labelled histamine, methyl histamine and it catabolites with imidazole acetic acid.