Development of an optimised method for the analysis of human blood plasma samples by atmospheric solids analysis probe mass spectrometry

Abstract

Analysis of small-molecule metabolites in plasma has the potential for development as a clinical diagnostic and prognostic tool. Atmospheric solids analysis probe mass spectrometry (ASAP-MS) is capable of performing rapid metabolite and small molecule fingerprinting, and has the potential for use in a clinical setting. Combining ASAP-MS data with a predictive model could provide clinicians with a rapid patient risk metric, anticipating disease progression and response to treatment, and thereby aiding in treatment decisions. In order to develop predictive models, experimental errors and uncertainties must be minimised, requiring a robust experimental protocol. In the present study we have performed ASAP-MS measurements on plasma samples from patients recruited for two prospective clinical studies: the Oxford Acute Myocardial Infarction (OxAMI) study; and the Oxford Abdominal Aortic Aneurysm (OxAAA) study. Through a carefully designed series of measurements, we have optimised the method of sample introduction, together with a number of key instrument and data acquisition parameters. Following the optimisation process, we are consistently able to record high quality mass spectra for plasma samples. Typical coefficients of variation for individual mass peaks are in the range from 20%–50%, overlapping with those obtained using more sophisticated LC-MS approaches. The measurement protocol optimises mass spectral quality and reproducibility, while retaining the simplicity of measurement required for use in a clinical setting. While the protocol was developed using plasma samples from two specific patient cohorts, the method can be generalised to any plasma measurements.