Development of a direct LC-ESI-MS method for the measurement of human serum carnosinase activity.

•Carnosinase activity is determined by LC–MS quantification of carnosine in serum.•Hydrolysis rate can also be measured for other natural histidine peptides.•Isotope dilution mass spectrometry (IDMS) allows reliable quantitation in serum.•HILIC column allows good retention for natural histidine dipeptides.•HILIC column allows MS-friendly analysis of organic solvent-rich supernatants.