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3A-O11-1625 PDF
イオンモビリティースペクトロメトリー質量分析によるDL-2-ヒドロキシグルタル酸の分離分析とイメージング
2-Hydroxyglutaric acid (2-HG) is a chiral metabolite whose enantiomers specifically accumulate in different diseases. For instance, monitoring of circulating D-2HG is known to be beneficial for early diagnosis and personalized treatments of acute myeloid leukemia (AML), in which an enantiomeric excess of D-2HG reflects the existence of various pathogenic mutations in isocitrate dehydrogenase genes. However, conventional methods using gas or liquid chromatography are unsuitable for routine clinical analysis because they require a long run time to separate DL-2HG. Here, we present a simple and rapid analytical method using a chiral derivatizing agent and field asymmetric waveform ion mobility spectrometry/mass spectrometry (FAIMS/MS). We compared three derivatization methods and found that a method using (S)-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidin-3-amine was better suitable for separation of DL-2HG. The lower detection limit was less than endogenous DL-2HG level in the serum, and the linear relationships between concentrations and signal intensities were observed at 8 - 500 nM with the correlation coefficients over 0.998. In addition, we applied the technique to another IMS/MS system and were able to visualize distribution of the enantiomers in the dried spots of standard solutions. These data would expand application of IMS for analyzing DL-2HG or other chiral molecules in clinical specimens.