Relative quantification of albumin and fibrinogen modifications by liquid chromatography tandem mass spectrometry in the diagnosis and monitoring of acute pancreatitis

•Sensitive detection of protein products of high abundance compared to enzymes.•Simple relative quantification approach without the need for internal standardisation.•Defined reference range for modified protein proportions.•Proteins with different degradation kinetics offer tracking and disease grading option.•Refined, robust LC–MS/MS method for measurement of a prospectively large analyte menu. The increasing availability of liquid chromatography tandem mass spectrometry (LC–MS/MS) in clinical laboratories provides the opportunity to replace or complement present underperforming immuno- and chemometric assays. Amylase and lipase show limited specificity and sensitivity for pancreatic inflammation and lack the capacity of monitoring the disease due to their short half-lives. Previous findings suggested that cleavage products of the pancreatic enzyme carboxypeptidase A could be a more suitable indicator for defining and classifying pancreatic inflammation. The plasma proteins albumin and β-fibrinogen were digested with trypsin and truncated forms (des-Leu-albumin, and des-Gln-β-fibrinogen) quantified against their non-truncated forms by LC–MS/MS. Four hundred fifty eight samples from 83 patients were used to evaluate the novel method and affirm its suitability for detecting acute pancreatitis. A robust, selective, precise and accurate LC–MS/MS method was set up to measure the proportion of truncated proteins. Reference ranges for the proportion of the truncated albumin and β-fibrinogen were from 2% to 9% and 3% to 25%, respectively. Acute pancreatitis patients had values above these ranges and were distinctly separated from reference control individuals. The longer circulating half-lives of albumin and fibrinogen compared to pancreatic enzymes themselves provide the potential to diagnose pancreatitis more specifically over a longer time period, to monitor the course of the disease, and to track recurrent complications. The wide range of the proportion and the differential half-life of both truncated proteins could also be used for assessing the severity of pancreatitis.