Determination of amino acid metabolic diseases from dried blood spots with a rapid extraction method coupled with nanoelectrospray ionization mass spectrometry

In this work, a rapid extraction method of methanol/water (95:5 v/v) with 0.1% formic acid was developed for extraction of amino acids from dried blood spots (DBS) for inherited metabolic diseases (IMDs). The combination of this extraction procedure with nanoelectrospray ionization mass spectrometry (nESI-MS) was used for the rapid analysis of amino acids. This approach with eliminating the chromatographic separation required only 2 min for the extraction of amino acids from DBS, which simplified the configuration and improved the timeliness. Dependence of the sensitivity on the operating parameters was systematically investigated. The LOD of 91.2–262.5 nmol/L and LOQ of 304–875 nmol/L which were lower than the cut-off values were obtained for amino acids within DBS. The accuracy was determined to be 93.82%–103.07% and the precision was determined to be less than 8.30%. The effectiveness of this method was also compared with the gold standard method (e.g., LC-MS/MS). The desalination mechanism was explored with interference mainly originated from the blood. These findings indicated that the rapid extraction procedure coupled with nESI-MS is capable of screening indicators for IMDs in complex biological samples.