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

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Abstract
Introduction: 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 providing rapid metabolite and small molecule fingerprinting and has the potential for use in a cinical setting. Such an approach could provide clinicians with a rapid patient risk metric, predicting disease progression and response to treatment, and thereby aiding in treatment decisions. Objectives: To develop a robust experimental protocol for performing ASAP-MS measurements on plasma samples. Methods: We 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. Over the course of a carefully designed series of measurements, we optimised the method of sample introduction, together with a number of key instrument and data acquisition parameters. Results: 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%, in line with those obtained by other researchersresearchers [1, 2] using more sophisticated LC-MS approaches. Conclusions: We have developed a measurement protocol for ASAP-MS measurements on plasma samples which optimises mass spectral quality and reproducibility, while still retaining the simplicity of measurement required for use in a clinical setting. While tested on samples from two specific cohorts of patients, the protocol can be employed in measurements on any blood plasma samples.

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