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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

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

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).

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

Chinese Summary  <22> 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


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DOI:

10.1631/jzus.B2100970

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On-line Access:

2022-07-06

Received:

2021-11-25

Revision Accepted:

2022-03-14

Crosschecked:

2022-07-06

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