氟磷谱定量核磁共振法进展综述

黄挺; 吴华鑫

doi:10.12338/j.issn.2096-9015.2023.0095

氟磷谱定量核磁共振法进展综述

doi: 10.12338/j.issn.2096-9015.2023.0095

黄挺^1,,
吴华鑫²

1.
中国计量科学研究院，北京 100029
2.
北京化工大学，北京 100029

基金项目: 中国计量科学研究院基本科研业务费项目（21-AKYZZ2120-21）。

详细信息

作者简介:
黄挺（1979-），中国计量科学研究院研究员，研究方向：化学计量、分析化学等，邮箱：huangting@nim.ac.cn

中图分类号: TB99
计量
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出版历程
- 收稿日期: 2023-03-30
- 录用日期: 2023-04-23
- 修回日期: 2023-05-19
- 网络出版日期: 2023-07-06

A Review on the Advancements in Quantitative Nuclear Magnetic Resonance Spectroscopy of Fluorine and Phosphorus

HUANG Ting^1
,,
WU Huaxin²

1.
National Institute of Metrology, Beijing 100029, China
2.
Beijing University of Chemical Technology, Beijing 100029, China

摘要

摘要: 定量核磁共振法(qNMR)作为一种选择性强、准确快捷的定量分析方法，广泛应用于有机化合物的纯度定值。它作为潜在基准方法，在国际计量比对中得到越来越广泛的关注与应用，而且最新的国际计量发展规划计划将其从传统的氢谱（¹H）扩展至氟谱、磷谱的技术领域。随着qNMR在代谢组学、环境分析和生理学研究等新的领域的应用，引入了天然产物、生物分子、蛋白质和代谢物等更复杂的分子和系统，使得常用的¹H-qNMR遇到很大挑战，因此基于氟（¹⁹F）和磷（³¹P）等具有核磁共振特性核的qNMR日益受到重视。与¹H-qNMR相比，氟谱和磷谱具有相近的灵敏度、更高的分辨能力，可以排除残留溶剂或水峰的干扰。介绍了¹⁹F-qNMR和³¹P-qNMR的特性优势、方法上的改进性和近年来在各领域的研究进展。在¹⁹F-qNMR和³¹P-qNMR方法学研究中，重点在具有溯源性的标准物质的研制、同轴插入内标方法、参数优化等方面。在应用领域，¹⁹F-qNMR重点集中于医药、材料、环境等领域，³¹P-qNMR集中于食品、医药、生物等领域。
- 计量学 /
- 定量核磁共振法 /
- 氟 /
- 磷 /
- 定量分析 /
- 有机化合物
Abstract: Quantitative Nuclear Magnetic Resonance (qNMR) stands as a selective, accurate, and prompt method for quantitative analysis, predominantly employed in purity assessments of organic compounds. Its potential as a primary method has generated burgeoning interest and applications in international metrological comparisons. The recent international metrological development strategy plans to extend its conventional scope from hydrogen spectroscopy (¹H) to fluorine and phosphorus spectroscopy. The incorporation of qNMR in new domains such as metabolomics, environmental analysis, and physiological research has introduced more intricate molecules and systems, like natural products, biomolecules, proteins, and metabolites, thereby challenging the standard ¹H-qNMR. This has led to an increased focus on qNMR methodologies based on other NMR-active nuclei such as fluorine (¹⁹F) and phosphorus (³¹P). These methodologies offer comparable sensitivity, enhanced resolution, and the ability to eliminate interference from residual solvents or water peaks relative to ¹H-qNMR. This review presents the distinctive advantages, methodological enhancements, and the latest research developments in ¹⁹F-qNMR and ³¹P-qNMR. Particular emphasis is placed on the development of traceable reference materials, coaxial internal standard insertion methods, and parameter optimization. The application domains of ¹⁹F-qNMR encompass medicine, materials, and environmental sciences, whereas ³¹P-qNMR is centered around food, medicine, and biological sectors.ound food, medicine, and biological sectors.
- metrology /
- quantitative nuclear magnetic resonance /
- fluorine /
- phosphorus /
- quantitative analysis /
- organic compounds

HTML全文

表 1 ¹⁹F-qNMR与类似技术的比较

Table 1. Comparison of ¹⁹F-qNMR with analogous techniques

类似技术	项目	¹⁹F-qNMR结果	类似技术结果	文献
¹H- qNMR	线性	0.9999	0.9999	^[18]
	精度	0.49%	0.82%	^[18]
	重复性	0.73%	0.62%	^[18]
	定量限(mg/mL)	1.34	1.02	^[18]
	平均值	93.1%	95.3%	^[18]
	RSD	0.73%	0.62%	^[18]
	回收率	98.7%	98.6%	^[18]
滴定性	当量重量(g/eq)	385	393	^[23]
气相色谱- 质谱法	雨水中的三氟乙酸(ng/L)	80	83	^[33]
		185	200	^[33]
		850	810	^[33]

下载: 导出CSV

表 2 ³¹P-qNMR与类似技术的比较

Table 2. Comparison of ³¹P-qNMR with analogous techniques

类似技术	项目	³¹P-qNMR 结果	类似技术结果	文献
液相色谱	磷霉素钙(mg/tablet)	511	516	^[36]
液相色谱	杂质A含量	2.12%	2.05%	^[36]
离子交换色谱	焦磷酸钠	96.01%	96.32%	^[39]
¹H- qNMR	TPPTS	58.51%	58.72	^[45]
二维薄层色谱	磷脂酰胆碱	25.3%	25.4%	^[47]
	磷脂酰乙醇胺	25.4%	21.8%	^[47]
	磷脂酰肌醇	13.6%	14.0%	^[47]
离子色谱法	PO₄³⁻ (g/kg)	3.50	3.34	^[49]
离子色谱法	P₂O₇⁴⁻ (g/kg)	0.61	0.59	^[49]
¹H- qNMR	索非布韦	99.44%	99.10%	^[50]

下载: 导出CSV

参考文献(53)

[1]	Working Group on Organic Analysis: Strategy 2021-2030. Consultative Committee for Amount of Substance-Metrology in Chemistry and Biology[EB/OL]. [2023-03-27].https://www.bipm.org/documents/20126/2071059/CCQM-OAWG+Strategy+document+2021-2030.pdf.
[2]	RIGGER R, RUCK A, HELLRIEGEL C, et al. Certified reference material for use in ¹H, ³¹P, and ¹⁹F quantitative NMR, ensuring traceability to the international system of units[J]. Journal of AoacInterna TionalVol, 2017, 100: 1365-1375.
[3]	DO N M, OLIVIER M A, SALISBURY JJ, et al. Application of quantitative ¹⁹F and ¹H NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate[J]. Anal Chem, 2011, 83: 8766-8771. doi: 10.1021/ac202287y
[4]	HENDERSON T J. Quantitative NMR spectroscopy using coaxial inserts containing a reference standard: purity determinations for military nerve agents[J]. Anal Chem, 2002, 74: 191-198. doi: 10.1021/ac010809+
[5]	MANIARA G, RAJAMOORTHI K, RAJAN S, et al. Method performance and validation for quantitative analysis by ¹H and ³¹P NM spectroscopy. Applications to analytical standards and agricultural Chemicals[J]. Anal Chem, 1998, 70: 4921-4928. doi: 10.1021/ac980573i
[6]	DEEN T S A, HIBBERT D B, HOOK J M, et al. Quantitative nuclear magnetic resonance spectrometryII. Purity of phosphorus-based agrochemicals glyphosate(N-(phosphonomethyl)-glycine) and profenofos(O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate)measured by ¹H and ³¹P QNMR spectrometry[J]. Analytica Chimica Acta, 2002, 474: 125-135. doi: 10.1016/S0003-2670(02)01017-6
[7]	AKINJOLE A, ALNAFISAH A S, COULIBALY F S, et al. Fluorine (¹⁹F) nuclear magnetic resonance spectroscopy for realtime maraviroc analysis from microparticulate systems[J]. Journal of Pharmaceutical Sciences, 2021, 00: 1-9.
[8]	韩智, 龚蕾, 王会霞, 等. 定量核磁共振磷谱在食品分析检测中的研究进展[J]. 食品与机械, 2021, 37(3): 207-212.
[9]	NISHIZAKI Y, LANKIN D C, CHEN S, et al. Accurate and precise external calibration enhances the versatility of quantitative NMR (qNMR)[J]. Anal Chem, 2011, 93, 2733-2741.
[10]	郎洁, 董燕, 王嫱智, 等. 核磁共振波谱内标法测定四氯虫酰胺标样的含量 [J]. 农药, 2020, 59(7): 499-501.
[11]	CASTAING-CORDIER T, LADROUE V, BESACIER F, et al. High-field and benchtop NMR spectroscopy for the characterization of new psychoactive substances[J]. Forensic Science International, 2021, 321: 110718. doi: 10.1016/j.forsciint.2021.110718
[12]	GERIG J T. Fluorine NMR [EB/OL]. [2023-03-29].https://www.biophysics.org/Portals/0/BPSAssets/Articles/gerig.pdf.
[13]	DALVIT C, KO S Y, VULPETTI A. Application of the rule of shielding in the design of novel fluorinated structuralmotifs and peptidomimetics[J]. Journal of Fluorine Chemistry, 2013, 152: 129-135. doi: 10.1016/j.jfluchem.2013.01.017
[14]	ARNTSON K E, POMERANTZ W C K. Protein-observed fluorine NMR: a biorthogonal approach for small molecule discovery[J]. Med Chem, 2016, 59: 5158-5171. doi: 10.1021/acs.jmedchem.5b01447
[15]	MISHRA N K, URICK A K, EMBER S W J, et al. Fluorinated aromatic amino acids are sensitive ¹⁹F NMR probes for bromodomain-ligand interactions[J]. ACS Chem, Biol, 2014, 9: 2755-2760. doi: 10.1021/cb5007344
[16]	MATTES A O, RUSSELL D, TISHCHENKO E, et al. Application of ¹⁹F quantitative NMR to pharmaceutical analysis[J]. Concepts MagnReson Part A, 2016, 45: 21422.
[17]	YU J, HALLAC RR, CHIGURU S. New frontiers and developing applications in ¹⁹F NMR[J]. Progress in Nuclear Magnetic Resonance Spectroscopy, 2013, 70: 25-49. doi: 10.1016/j.pnmrs.2012.10.001
[18]	LIU Y, LIU Z, YANG H, et al. Direct Comparison of ¹⁹F qNMR and ¹H qNMR by Characterizing Atorvastatin Calcium Content[J]. Journal of Analytical Methods in Chemistry, 2016, 5: 5-10.
[19]	VLASIOU M, DROUZAC. ¹⁹F NMR for the speciation and quantification of theOH-molecules in complex matrices[J]. Anal Methods, 2015, 7: 3680-3684. doi: 10.1039/C5AY00178A
[20]	LIU C, SONG C, JIA W, et al. The application of ¹⁹F NMR spectroscopy for the analysis of fluorinated new psychoactive substances (NPS)[J]. Forensic Science International, 2022, 340: 111450. doi: 10.1016/j.forsciint.2022.111450
[21]	AYOTTE Y, WOO S, LAPLANTE S R. Practical considerations and guidelines for spectral referencing for fluorine NMR ligand screening[J]. ACS Omega, 2022, 7: 13155-13163. doi: 10.1021/acsomega.2c00613
[22]	KADDOURI A E, PERRIN L, JEAN B, et al. Investigation of perfluorosulfonic acid ionomer solutions by ¹⁹F NMR and DLS: establishment of an accurate quantification protocol[J]. Polymer Physics, 2016, 54: 2210-2222. doi: 10.1002/polb.24130
[23]	MOGHIMI A, OMRANI I, KHANMIRI R H, et al. Determination of NCO content of the urethane prepolymers by ¹⁹F NMR spectroscopy[J]. Polymer Testing, 2014, 33: 30-33. doi: 10.1016/j.polymertesting.2013.11.002
[24]	YAMAZAKI T, SAITO T, IHARA T. A new approach for accurate quantitative determination using fluorine nuclear magnetic resonance spectroscopy[J]. J Chem Metrol, 2017, 11: 16-22. doi: 10.25135/jcm.3.17.03.036
[25]	NASR JJ, SHALAN S. Validated ¹H and ¹⁹F nuclear magnetic resonance for the quantitative determination of the hepatitis C antiviral drugs sofosbuvir, ledipasvir, and daclatasvir in tablet dosage forms[J]. Microchemical Journal, 2020, 152: 104437. doi: 10.1016/j.microc.2019.104437
[26]	WANG D, PARK J H, ZHENG J, et al. Multiphase drug distribution and exchange in oil-in-Water nano emulsion revealed by high-resolution ¹⁹F qNMR[J]. Mol Pharmaceutics, 2022, 19: 2142-2150. doi: 10.1021/acs.molpharmaceut.2c00025
[27]	邓冬艳, 宋红杰, 齐悦. 核磁共振氟谱法测定氟他胺含量的实验设计 [J]. 实验室研究与探索, 2019, 38(6): 30-37.
[28]	杨百勤, 孔二丽, 薛潇迪, 等. 采用核磁共振氟谱定性与定量分析盐酸氟西汀 [J]. 药学学报, 2012, 47(5): 630-633.
[29]	史艺文, 李钦, 林崇熙. 核磁共振氟谱对五氟利多的定量分析 [J]. 河南大学学报(医学版), 2015, 34(4): 252-255.
[30]	MA S, CHEN Q, JOGENSEN F H, et al. ¹⁹F NMR studies of Nafion™ ionomer adsorption on PEMFC catalysts and supporting carbons[J]. Solid State Ionics, 2007, 178: 1568-1575. doi: 10.1016/j.ssi.2007.10.007
[31]	叶怀英, 孟庆文, 余国军, 等. 核磁共振技术在含氟聚合物定量分析中的应用 [J]. 分析与检测, 2022, 28(5): 29-33.
[32]	BHAT A P, POMERANTZ W C K, ARNOLD W A. Finding fluorine: photoproduct formation during the photolysis of fluorinated pesticides[J]. Environ Sci Technol, 2022, 56: 12336-12346. doi: 10.1021/acs.est.2c04242
[33]	ELLIS D A, MARTIN J W, MUIR D C G, et al. Development of an ¹⁹F NMR method for the analysis of fluorinated acids in environmental water samples[J]. Anal Chem, 2000, 72: 726-731. doi: 10.1021/ac9910280
[34]	AKHDAR A, ANDANSON J, FAURE S, et al. Application of quantitative ¹H and ¹⁹F NMR to organometallics[J]. Journal of Organometallic Chemistry, 2021, 950: 121991. doi: 10.1016/j.jorganchem.2021.121991
[35]	AGRAHARI V, MENG J, PUROHIT SS, et al. Real-time analysis of tenofovir release kinetics using quantitative phosphorus (³¹P) nuclear magnetic resonance spectroscopy[J]. Journal of Pharmaceutical Sciences, 2017, 106: 3005-3015. doi: 10.1016/j.xphs.2017.03.043
[36]	JIANG H, CHEN H, CAI N, et al. Quantitative 31P-NMR spectroscopy for the determination of fosfomycin and impurity A in pharmaceutical products of fosfomycin sodiumor calcium[J]. MagnReson Chem, 2015, 53: 454-459.
[37]	黄挺, 王静羽, 万康妮. 去除杂质干扰的定量核磁共振法进展综述 [J]. 计量科学与技术, 2022, 66(6): 26-30.
[38]	MICHAEL M A, BERKOWITZ H D, GROSS G M, et al. ³¹P nuclear magnetic resonance spectroscopy: Noninvasive biochemical analysis of the ischemic extremity[J]. J Vasc Surg, 1986, 3: 411-420.
[39]	GARD D R, BURQUIN J C, GARD J K, et al. Quantitative Analysis of Short-Chain Phosphates by Phosphorus-31 Nuclear Magnetic Resonance and Interlaboratory Comparison with Infrared and Chromatographic Methods[J]. Anal Chem, 1992, 64: 557-561. doi: 10.1021/ac00029a020
[40]	MARTINO R, GILARD V, DESMOULIN D, et al. Fluorine-19 or phosphorus-31 NMR spectroscopy: A suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs[J]. J Pharmaceut Biomed, 2005, 38: 871-891. doi: 10.1016/j.jpba.2005.01.047
[41]	黄挺, 张伟, 全灿, 等. 定量核磁共振新方法在纯度定值的应用 [J]. 计量技术, 2018(9): 8-9.
[42]	MATSUMI R, HELLRIEGEL C, SCHOENENBERGER B, et al. Biocatalytic asymmetric phosphorylation of mevalonate[J]. RSC Adv, 2014, 4: 12989-12994. doi: 10.1039/c4ra01299b
[43]	DEREWINSKI M, SARV P, SUN X, et al. Reversibility of the Modification of HZSM-5 with Phosphate Anions[J]. J Phys Chem C, 2014, 118: 6122-6131. doi: 10.1021/jp4053677
[44]	ATANASSOVA M, KURTEVA V. Peculiar synergistic extraction behavior of Eu(III) in ionic liquids: benzoyl acetone and CMPO fusion[J]. Sep Purif Technol, 2017, 183: 226-236. doi: 10.1016/j.seppur.2017.03.033
[45]	梁春杰, 孟庆春, 徐晓婷, 等. 基于¹ H - NMR、³¹ P - NMR的三苯基膦三间磺酸钠定量分析研究 [J]. 分析测试学报, 2020, 39(8): 1018-1022.
[46]	BELMONTE-SÁNCHEZ J R, AGUILERA-SÁEZ L M, ROMERO-GONZÁLEZ R, et al. Determination of etidronic acid in vegetable-washing water by a simple and validated quantitative ³¹P nuclear magnetic resonance method[J]. Microchem J, 2019, 150: 104083 doi: 10.1016/j.microc.2019.104083
[47]	KATO T, NISHIMIYA M, KAWATA A, et al. Quantitative ³¹P NMR Method for Individual and Concomitant Determination of Phospholipid Classes in Polar Lipid Samples[J]. J Oleo Sci, 2018, 67(1): 1279-1289.
[48]	LOENING N M, CHAMBERLIN A M, ZEPEDA A G, et al. Quantification of phosphocholine and glycerophosphocholine with ³¹P edited ¹H NMR spectroscopy[J]. NMR Biomed, 2005, 18: 413-420. doi: 10.1002/nbm.973
[49]	韩智, 江丰, 周密, 等. 核磁共振磷谱定量测定肉制品中磷酸盐的含量 [J]. 食品工业科技, 2021, 42(9): 275-280.
[50]	UCHIYAMA N, KIYOTA K, HOSOE J, et al. Quantitative ³¹P-NMR for Purity Determination of Sofosbuvir and Method Validation[J]. Chem Pharm Bull, 2022, 70(12): 892-900. doi: 10.1248/cpb.c22-00639
[51]	BETTJEMANB I, HOFMAN K A, BURGESS E J, et al. Seafood Phospholipids: Extraction Efficiency and Phosphorous Nuclear Magnetic Resonance Spectroscopy (³¹P NMR) Profiles[J]. J Am Oil Chem Soc, 2018, 95: 779-786. doi: 10.1002/aocs.12086
[52]	WANG Y, YANG B, WAN B, et al. Degradation of Black Phosphorus: A Real-Time ³¹P NMR Study[J]. 2D Mater, 2016, 3: 035025. doi: 10.1088/2053-1583/3/3/035025
[53]	MAZUMDER A, KUMAR A, PUROHIT A K, et al. A high-resolution phosphorus-31 nuclear magnetic resonance (NMR) spectroscopic method for the non-phosphorus markers of chemical warfare agents[J]. Anal Bioanal Chem, 2012, 402: 1643–1652. doi: 10.1007/s00216-011-5561-7