Simultaneous quantification of 11 pivotal metabolites in neural tube defects by HPLC-electrospray tandem mass spectrometry |
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Authors: | Wang Yong Zhang Hong-Yang Liang Qiong-Lin Yang Hui-Hua Wang Yi-Ming Liu Qing-Fei Hu Ping Zheng Xiao-Ying Song Xin-Ming Chen Gong Zhang Ting Wu Jian-Xin Luo Guo-An |
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Institution: | School of Pharmaceutics, East-China University of Science & Technology, People's Republic of China. |
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Abstract: | One-carbon metabolism that involves folate metabolism and homocysteine metabolism plays a powerful role in embryonic development. Any impairment to this metabolism during the neurulation process would trigger the occurrence of neural tube defects (NTDs). The great importance of one-carbon metabolism necessitates the establishment of methodology to determine the relative compounds involved in the metabolic cycles. We have developed a sensitive method for measurement of 11 pivotal compounds by using high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS) in sera of pregnant women. Use of an aqueous chromatography column increased retention time and separation of the polar compounds in the system, resulting in fewer co-elution and interference from the other compounds that can lead to ion suppression. Calibration curves suitable for the analysis of maternal serum were linear (r(2)>0.997) with limits of detection from 0.05 to 1ng/mL. Intra-day coefficients of variation (CVs) and inter-day CVs were both lower than 11%. With the developed method, 96 serum samples including 46 cases and 50 controls were analyzed. The established method provided a reliable method for quantifying most of the compounds involved in the one-carbon metabolism simultaneously, thus made it possible to elucidate NTDs with multiple factors instead of one single and provided a solid foundation for the diagnosis and prevention of NTDs as well as some other one-carbon metabolism related diseases. |
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