Charged Water Enables the Determination of Inherited Metabolic Diseases by Mass Spectrometry.

Abstract

Inherited metabolic diseases (IMDs) have drawn considerable attention due to their disruption of normal metabolic pathways. However, conventional extraction techniques are predominantly offline and time-consuming, making them inadequate for the rapid screening required in clinical settings. We developed a novel method involving the extraction of dried sample spots, which are subsequently mixed with charged water (H2O) before infusion electrospray ionization-mass spectrometry analysis. This method was successfully applied for the simultaneous determination of nine amino acid and seven acylcarnitine indicators in dried serum, blood, and urine spots, covering the majority of IMDs routinely screened in hospitals. Compared with conventional approaches, the sensitivity of the new technique improved by nearly threefold, and in some cases, by up to an order of magnitude. The method's clinical applicability was further confirmed through comparison with the recommended liquid chromatography-tandem mass spectrometry platform and was evaluated using serum samples from three healthy individuals. Additionally, the effect of charged H2O was investigated in detail. A potential mechanism was proposed, suggesting that positively charged H2O enhances ionization by repelling inorganic salts and increasing the density of charges around the target analytes. Although the high surface tension of H2O can, to some extent, suppress ionization, the incorporation of charged H2O in this workflow boosted analytical sensitivity. Overall, this study introduces a simple, rapid, and highly efficient method for the clinical screening of amino acid and acylcarnitine-related IMDs, offering a promising alternative to conventional techniques.