Full Text:  <786>

Suppl. Mater.: 

Summary:  <319>

CLC number: 

On-line Access: 2022-07-06

Received: 2021-11-25

Revision Accepted: 2022-03-14

Crosschecked: 2022-07-06

Cited: 0

Clicked: 886

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Cuirong SUN

https://orcid.org/0000-0002-4479-8013

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)


Detection, isolation, and characterization of a novel impurity from several folic acid products


Author(s):  Qirong SHEN, Quan HE, Yuanjiang PAN, Cuirong SUN

Affiliation(s):  College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; more

Corresponding email(s):  suncuirong@zju.edu.cn

Key Words:  Impurity; Folic acid; Multidimensional NMR; QTOF-HRMS; Identification


Share this article to: More <<< Previous Paper|Next Paper >>>

Qirong SHEN, Quan HE, Yuanjiang PAN, Cuirong SUN. Detection, isolation, and characterization of a novel impurity from several folic acid products[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2100970

@article{title="Detection, isolation, and characterization of a novel impurity from several folic acid products",
author="Qirong SHEN, Quan HE, Yuanjiang PAN, Cuirong SUN",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2100970"
}

%0 Journal Article
%T Detection, isolation, and characterization of a novel impurity from several folic acid products
%A Qirong SHEN
%A Quan HE
%A Yuanjiang PAN
%A Cuirong SUN
%J Journal of Zhejiang University SCIENCE B
%P 597-606
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2100970"

TY - JOUR
T1 - Detection, isolation, and characterization of a novel impurity from several folic acid products
A1 - Qirong SHEN
A1 - Quan HE
A1 - Yuanjiang PAN
A1 - Cuirong SUN
J0 - Journal of Zhejiang University Science B
SP - 597
EP - 606
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2100970"


Abstract: 
Folic acid belongs to the group of water-soluble B vitamins and naturally exists in multiple forms in a wide variety of foods such as legumes, vegetables, liver, and milk (Iyer and Tomar, 2009; Lyon et al., 2020). It is involved in many biochemical reactions critical for cell division, such as purine and pyrimidine biosynthesis, DNA/RNA biosynthesis, and amino acid metabolism (Iyer and Tomar, 2009). Mammals cannot synthesize folic acid and thus they must acquire it from food. Although folic acid is ubiquitous in foods, folic acid deficiency still often occurs due to various causes such as unhealthy diet (Hildebrand et al., 2021; Iimura et al., 2022), disease-related malabsorption (Arcot and Shrestha, 2005), medication-related depletion (Arcot and Shrestha, 2005), or vitamin B12 deficiency (Fishman et al., 2000). Folic acid deficiency has been associated with several health problems, such as anemia (Carmel, 2005; Bailey and Caudill, 2012), cancer (Duthie, 1999), cardiovascular diseases (Wald et al., 2002), neural tube defects in newborns (van der Put et al., 2001), neuropsychiatric dysfunction (Shea et al., 2002), depression (Falade et al., 2021), inflammatory diseases (Suzuki and Kunisawa, 2015; Jones et al., 2019), and eye diseases (Sijilmassi, 2019). To prevent folic acid deficiency, its daily intake (400 ?g/d) has been recommended for adults in the European Union, and its increased intake (600 ?g/d) is advised for women before and during pregnancy (FAO/WHO, 2002; IOM, 2004). The New Zealand government mandated the fortification of non-organic wheat flour with folic acid in July 2021, and the UK government mandated the fortification of non-wholemeal wheat flour with folic acid in September 2021 (Haggarty, 2021).

叶酸产品中一种新杂质的检测、分离和结构表征

沈杞容1,3,何佺1,潘远江2,孙翠荣1
1浙江大学药学院,中国杭州,310058
2浙江大学化学系,中国杭州,310027
3杭州仟源保灵药业有限公司,中国杭州,310018
概要:叶酸是一种重要的营养物质,常用于孕妇和婴幼儿人群的食品强化和营养补充。在叶酸产品的生产和储运过程中,常会产生一些杂质,其中大部分已获得结构鉴定,其中一些已被收录入药典。本研究报道了一种新的叶酸杂质K,该杂质存在于多种叶酸产品中。本研究采用制备型高效液相色谱对该杂质进行了成功分离,并采用多维核磁共振谱、高分辨质谱、傅里叶红外光谱和紫外光谱等分析手段,对其化学结构进行了鉴定。结果显示,该杂质是药典记载的叶酸杂质D的同分异构体,经结构分析,推测其为叶酸杂质G的水解产物。

关键词组:叶酸;杂质;核磁共振;高分辨质谱

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Araya-MaturanaR, Pessoa-MahanaH, Weiss-LópezB, 2008. Very long-range correlations (nJC,H n > 3) in HMBC spectra. Natl Prod Commun, 3(3):445-450.

[2]ArcotJ, ShresthaA, 2005. Folate: methods of analysis. Trends Food Sci Technol, 16(6-7):253-266.

[3]BaileyLB, CaudillMA, 2012. Folate. In: Erdman JW Jr, Macdonald IA, Zeisel SH (Eds.), Present Knowledge in Nutrition, 10th Ed. Wiley-Blackwell, Washington, p.321-342.

[4]CarmelR, 2005. Folic acid. In: Shils ME, Shike M, Ross AC, et al. (Eds.), Modern Nutrition in Health and Disease, 10th Ed. Lippincott Williams & Wilkins, Philadelphia, p.470-481.

[5]ClaridgeTDW, 2008. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed. Pergamon Press, Oxford, United Kingdom.

[6]DántolaML, DenofrioMP, ZurbanoB, et al., 2010. Mechanism of photooxidation of folic acid sensitized by unconjugated pterins. Photochem Photobiol Sci, 9(12):1604-1612.

[7]DántolaML, UrrutiaMN, ThomasAH, 2018. Effect of pterin impurities on the fluorescence and photochemistry of commercial folic acid. J Photochem Photobiol B Biol, 181:157-163.

[8]DuthieSJ, 1999. Folic acid deficiency and cancer: mechan

[9]isms of DNA instability. Br Med Bull, 55(3):578-592.

[10]FaladeJ, OnaolapoAY, OnaolapoOJ, 2021. The role of folate-supplementation in depression: a narrative review. Curr Psychopharmacol, 10(2):115-122.

[11]FAO/WHO (Food and Agriculture Organization of the United Nations and the World Health Organization), 2002. Human Vitamin and Mineral Requirements. Report of a Joint FAO/WHO Expert Consultation. FAO, Rome, Italy.

[12]FishmanSM, ChristianP, WestKP, 2000. The role of vitamins in the prevention and control of anaemia. Public Health Nutr, 3(2):125-150.

[13]HaggartyP, 2021. UK introduces folic acid fortification of flour to prevent neural tube defects. Lancet, 398(10307):1199-1201.

[14]HildebrandLA, DumasB, MilrodCJ, et al., 2021. Folate deficiency in an urban safety net population. Am J Med, 134(10):1265-1269.

[15]IimuraY, KurokawaT, KanemotoY, et al., 2022. Severe thrombocytopenia induced by chemotherapy after total gastrectomy: a report of three cases. Int J Clin Pharmacol Ther, 60:36-40.

[16]IOM, 2004. Dietary reference intakes (DRIs): recommended intakes for individuals, vitamins. The National Academies Press, Washington.

[17]IyerR, TomarSK, 2009. Folate: a functional food constituent. J Food Sci, 74(9):R114-R122.

[18]JonesP, LucockM, ScarlettCJ, et al., 2019. Folate and Inflammation‍‒‍links between folate and features of inflammatory conditions. J Nutr Intermed Metab, 18:100104.

[19]KłaczkowG, AnuszewskaEL, 2006. Determination of impurities in pharmaceutical preparations containing folic acid. Acta Pol Pharm, 63(5):391-394.

[20]LucockM, 2000. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab, 71(1-2):121-138.

[21]LyonP, StrippoliV, FangB, et al., 2020. B vitamins and one-carbon metabolism: implications in human health and disease. Nutrients, 12(9):2867.

[22]MüllerL, SingerT, 2009. EMS in Viracept—the course of events in 2007 and 2008 from the non-clinical safety point of view. Toxicol Lett, 190(3):243-247.

[23]Pharmaffiliates Analytics and Synthetics P. Ltd., 2021. Folic acid and its impurities. https://www.‍pharmaffiliates.‍com/en/parentapi/folic-acid-impurities

[24]RossiC, DonatiA, UlgiatiS, et al., 1992. Structural investigation of folic acid by NMR proton relaxation and molecular mechanics analysis. Bull Magn Reson, 14(1-4):181-185.

[25]SheaTB, Lyons-WeilerJ, RogersE, 2002. Homocysteine, folate deprivation and Alzheimer neuropathology. J Alzheimers Dis, 4(4):261-267.

[26]SijilmassiO, 2019. Folic acid deficiency and vision: a review. Graefes Arch Clin Exp Ophthalmol, 257(8):1573-1580.

[27]SuzukiH, KunisawaJ, 2015. Vitamin-mediated immune regulation in the development of inflammatory diseases. Endocr Metab Immune Disord Drug Targets, 15(3):212-215.

[28]CommissionThe European Pharmacopoeia, 2018. Folic Acid Hydrate. In: The European Pharmacopoeia. EDQM Council of Europe, Strasbourg, France, p.5662-5663.

[29]van der PutNMJ, van StraatenHWM, TrijbelsFJM, et al., 2001. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med, 226(4):243-270.

[30]WaldDS, LawM, MorrisJK, 2002. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ, 325(7374):1202-1206.

[31]WenGJ, 2017. The Process for Preparation of Folic Acid. MS Thesis, Southeast University, Nanjing, China(in Chinese).

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE