Simultaneous determination of sarcosine and its related metabolites by gas chromatography-tandem mass spectrometry for prostate cancer diagnosis
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Date
2018-10-16
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Abstract
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.
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Keywords
Gas chromatography-tandem mass spectrometry, Sarcosine, Alanine, Glycine, Creatinine, MRM