Simultaneous determination of sarcosine and its related metabolites by gas chromatography-tandem mass spectrometry for prostate cancer diagnosis

Abstract

© 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved. Shortly after sarcosine was delineated as a potential biomarker for prostate cancer in 2009, a variety of analytical methods for clinical application were developed. Moreover, higher uptake of glycine in the mitochondria also played a role in cancer proliferation. A major constraint in the accurate quantification of sarcosine was the interference of the two isomers, α-alanine and β-alanine, using chromatographic separation techniques. Accordingly, we aimed to develop an analytical method for determining sarcosine and its related metabolites (α-and β-alanine, glycine and creatinine) under the same conditions by gas chromatography-tandem mass spectrometry (GCMS/MS). BSTFA + 1 % TMCS was used for silylation, and GC-MS/MS conditions were optimized for the target analytes. The unique transition ions of sarcosine, α-and β-alanine, glycine and creatinine set up in MRM acquisition were m/z 116 → 73, 190 → 147, 176 → 147, 176 → 147 and 100 → 73, respectively. This newly developed method was successfully validated to apply in clinical settings with low limits of detection (0.01-0.03 µg•mL-1), high correlations (R2 > 0.99), great accuracy (88 – 110 % recovery), and notable precision (RSD < 10 %). All TMS derivatives were > 80 % stable for up to 2 h after derivatization and analyzing during this period promises to achieve an accurate result. Monitoring the five-substance profile could enhance prospects for early diagnosis of prostate cancer.