title: Quantification of folate metabolites in serum using ultraperformance liquid chromatography tandem mass spectrometry.
abstract: Folate deficiency is considered a risk factor for many diseases such as cancer, congenital heart disease and neural tube defects (NTDs). There is a pressing need for more methods of detecting folate and its main metabolites in the human body. Here, we developed a simple, fast and sensitive ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) method for the simultaneous quantifications of folate metabolites including folic acid, 5-methyltetrahydrofolate (5-MeTHF), 5-formyltetrahydrofolate (5-FoTHF), homocysteine (Hcy), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). The method was validated by determining the linearity (r(2)>0.998), sensitivity (limit of detection ranged from 0.05 to 0.200ng/mL), intra- and inter-day precision (both CV<6%) and recovery (each analyte was >90%). The total analysis time was 7min. Serum samples of NTD-affected pregnancies and controls from a NTD high-risk area in China were analyzed by this method, the NTD serum samples showed lower concentrations of 5-MeTHF (P<0.05) and 5-FoTHF (P<0.05), and higher concentrations of Hcy (P<0.05) and SAH (P<0.05) compared with serum samples from controls, consistent with a previous study. These results showed that the method is sensitive and reliable for simultaneous determination of six metabolites, which might indicate potential risk factors for NTDs, aid early diagnosis and provide more insights into the pathogenesis of NTDs.
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Chines Academy of Inspection & Quarantine, Beijing 100023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China. Electronic address: fywjh@163.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: niub2004@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D002955:Leucovorin / Q000097:blood / Q000378:metabolism; D057230:Limit of Detection; D009436:Neural Tube Defects / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013763:Tetrahydrofolates / Q000097:blood / Q000378:metabolism
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D002955:Leucovorin; C005984:5-methyltetrahydrofolate
keywords: Folic acid; Neural tube defects; One-carbon metabolism; UPLC/MS/MS