Simultaneous quantification of 11 pivotal metabolites in neural tube defects by HPLC-electrospray tandem mass spectrometry.
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.
Wang
Yong
Y
School of Pharmaceutics, East-China University of Science & Technology, People's Republic of China.
Zhang
Hong-Yang
HY
Liang
Qiong-Lin
QL
Yang
Hui-Hua
HH
Wang
Yi-Ming
YM
Liu
Qing-Fei
QF
Hu
Ping
P
Zheng
Xiao-Ying
XY
Song
Xin-Ming
XM
Chen
Gong
G
Zhang
Ting
T
Wu
Jian-Xin
JX
Luo
Guo-An
GA
D002138:Calibration; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D007202:Indicators and Reagents; D007231:Infant, Newborn; D009436:Neural Tube Defects / Q000378:metabolism* / Q000517:prevention & control; D011247:Pregnancy; D011786:Quality Control; D015203:Reproducibility of Results; D012307:Risk Factors; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013763:Tetrahydrofolates / Q000097:blood
D006397:Hematinics; D007202:Indicators and Reagents; D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid