Automated Metadata Review to Support Result Release in Quantitative Liquid Chromatography Coupled With Tandem Mass Spectrometry Applications

ABSTRACT Quantitative multi‐target analysis of biological samples using isotope‐dilution liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) is widely applied in laboratory diagnostics and life sciences now. These analyses generate a large amount of metadata (e.g. ion ratios, peak width, etc.) that must be reviewed before results can be released. Until now, these complex and time‐consuming tasks are performed mainly by technicians without dedicated software support. To explore whether practical tools for supporting result validation and release can be developed using standard spreadsheet software. A script, named MS Excel‐based evaluation macro (MSVal), was developed in Microsoft Excel. Data sets from the quantification software of an LC‐MS/MS system are imported into this tool. Validation criteria as quality assurance rules for analytical series and individual samples are defined within MSVal. The tool's functionality was evaluated using datasets from cystic fibrosis transmembrane conductance regulator (CFTR)‐modulator therapeutic drug monitoring (TDM) analytical series. After importing raw MS data, MSVal generates a list of results that meet predefined validation criteria. MSVal also produces a validation report for each analytical series. Results that do not meet validation criteria are highlighted and must be specifically addressed by the operator during the release process. MSVal was successfully tested with real‐world datasets. The development of software applications to support validation and result release in quantitative isotope‐dilution LC‐MS/MS analysis is feasible using standard software. Further refinement and progression toward commercial solutions appear valuable to close a significant gap in the clinical application of mass spectrometry.