Objective: To establish a 1H quantitative nuclear magnetic resonance method (1H qNMR) for the determination of the ethoxy content in ethyl cellulose. This method avoids the shortcomings like time-consuming, labor-intensive, demanding in terms of analyst’s expertise, high reagent pollution, and unsatisfactory accuracy and reproducibility from gas chromatography method. Methods: 1H qNMR of ethyl cellulose were obtained in chloroform-d with a Bruker Avance Ⅲ 600 NMR spectrometer. The relaxation delay time was 15 s, the flip angle was 90°, the acquisition time was 5 s, and the number of scans was 64. The method did not involve the internal standard. It is based on the 1H NMR signal area of methyl protons (δ=1.15), the 1H NMR peak area of methylene and methine protons (δ=3.0-4.6) in ethyl cellulose and their number of protons. Results: The ethoxy content of ethyl cellulose (batch No. 0882117001) determined by the 1H NMR relative quantitative method was 49.5% with RSD 0.6% (n=6). The sample solution was stable for at least three days. The method was rugged at specified temperature (298, 300 K) and concentration between 24.32 mg·mL-1 and 30.77 mg·mL-1. The results agreed well with the ethoxy content of 49.2% as determined by gas chromatography. Conclusion: The 1H NMR relative quantification method, without involving an internal standard, is simple and rapid. Its accuracy and precision are suitable for its intended use, i.e. determination of ethoxy content in pharmaceutical grade ethyl cellulose.
[1] RIZZO V, PINCIROLI V. Quantitative NMR in synthetic and combinatorial chemistry[J].J Pharm Biomed Anal, 2005, 38(5):851
[2] 仲艳, 李家春, 王志霞,等. 定量核磁共振波谱法测定二对甲苯磺酸缘生替尼对照品的含量[J].药物分析杂志, 2019, 039(003):432
ZHONG Y, LI JC, WANG ZX, et al. Determination of yunsintinib ditosylate reference subsfance by 1HH quantitative nuclear magnetic resonance spectroscopy[J].Chin J Pharm Anal, 2019, 39(3):432
[3] 张芬芬, 蒋孟虹, 沈文斌, 等. 定量核磁共振(QNMR)技术及其在药学领域的应用进展[J].南京师范大学学报(工程技术版), 2014(2):8
ZHANG FF, JIANG MH, SHEN WB, et al. Progress in quantitative nuclear magnetic resonance technology in pharmaceutical applications[J].J Nanjing Norm Univ (Eng Technol Ed), 2014(2):8
[4] 中华人民共和国药典 2015 年版. 四部[S].2015: 52
ChP 2015. Vol IV [S].2015: 52
[5] MALZ F, JANCKE H. Validation of quantitative NMR[J].J Pharm Biomed Anal, 2005, 38(5):813
[6] 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
YANG BQ, KONG EL, XUE XD, et al. Qualitative and quantitative analysis of fluoxetine hydrochloride by 19F NMR[J].Acta Pharm Sin, 2012, 47(5):630
[7] 张光华, 朱军峰, 徐晓凤. 纤维素醚的特点、制备及在工业中的应用[J].纤维素科学与技术, 2006, 14(1):60
ZHANG GH, ZHU JF, XU XF. Properties and applications of cellulose ethers[J].J Cellulos Sci Technol, 2006, 14(1):60
[8] REKHI GS, JAMBHEKAR SS. Ethylcellulose-A polymer review[J].Drug Dev Ind Pharm, 1995, 21(1):61
[9] CUNDIFF RH, MARKUNAS PC. Determination of alkoxyl groups by nonaqueous titration[J].Anal Chem, 1961, 33(8):1028
[10] 付时雨, 谢传龙, 张亮亮, et al. 乙基纤维素乙氧基含量的顶空气相色谱法测定[J].华南理工大学学报(自然科学版), 2011, 39(11):17
FU SY, XIE CL, ZHANG LL, et al. Determination of ethoxyl content of ethyl cellulose by means of headspace gas chromatography[J].J South China Univ Technol (Nat Sci Ed), 2011, 39(11):17
[11] 赵大箐, 董雪艳. FTIR法测定EC乙氧基含量[J].纤维素醚工业, 2002, 10(1):23
ZHAO DJ, DONG XY. Determination of EC ethoxy content by FTIR[J].Cellulos Ethers Ind, 2002, 10(1):23
[12] KONO H. Determination of mole fractions of ethyl-cellulose-containing monomers by NMR[J].Carbohydrate Res, 2017, 445:51
[13] 张尧, 骆霞, 彭欢, 等. 一种检测乙基纤维素乙氧基含量的方法[P]. CN.106370620A.20160830[20170201]
ZHANG Y, LUO X, PENG H, et al. A method for the determination of ethoxyl content of ethyl cellulose[P]. CN.106370620A.20160830[20170201]
[14] EASTERBROOK WC, HAMILTON JB. The micro-determination of alkoxyl values in cellulose esters[J].Analyst, 1953, 78(930):551
[15] SAMSEL E, MCHARD J. Determination of alkoxyl groups in cellulose ethers[J].Ind Engin Chem Anal Edit, 1942, 14(9):750
[16] CUNDIFF RH, MARKUNAS PC. Determination of alkoxyl groups by nonaqueous titration[J].Anal Chem, 1961, 33(8):1028
[17] US 41-NF36[S].2018:8485
[18] REKHI GS, JAMBHEKAR SS. Ethylcellulose-a polymer review[J].Drug Dev Ind Pharm, 1995, 21(1):61
[19] 周晓力, 曾月林, 南楠, 等. 1H qNMR定量测定二乙酰吗啡对照品的含量[J].药物分析杂志, 2015, 35(5):906
ZHOU XL, ZENG YL, NAN N, et al. Determination of diacetylmorphine reference substance by 1H qNMR[J].Chin J Pharm Anal, 2015,35(5):906
[20] GOTTLIEB HE, KOTLYAR V, NUDELMAN A. NMR chemical shifts of common laboratory solvents as trace impurities[J].J Org Chem, 1997, 62(21):7512
[21] BEYER T, DIEHI B, RRANDEL G, et al. Quality assessment of unfractionated heparin using 1H nuclear magnetic resonance spectroscopy[J].J Pharm Biomed Anal, 2008, 48(1):13
[22] 黄挺, 张伟, 全灿,等. 定量核磁共振法研究进展[J].化学试剂, 2012, 34(4):327
HUANG T, ZHANG W, QUAN C, et al. Review on quantitative nuclear magnetic resonance[J].Chem Reagents, 2012, 34(4):327
[23] 刘英, 胡昌勤. 核磁共振在抗生素药物定量分析中的应用[J].药物分析杂志, 2001,21(6):447
LIU Y, HU CQ. Application of NMR in quantitative analysis of antibiotics[J].Chin J Pharm Anal, 2001,21(6):447
[24] POSTMA A, DAVIS TP, DONOVAN AR, et al. A simple method for determining protic end-groups of synthetic polymers by 1H NMR spectroscopy[J].Polymer, 2006, 47(6):1899
[25] BHARTI SK, ROY R. Quantitative 1H NMR spectroscopy[J].Trends Anal Chem, 2012, 35(1):5
[26] LARIVE CK, JAYAWICKRAMA D, ORFI L. Quantitative analysis of peptides with NMR spectroscopy[J].Appl Spectrosc, 1997, 51(10):1531
[27] PAULI GF, JAKI BU, LANKIN DC. A Routine experimental protocol for qhnmr illustrated with taxol [J].J Nat Prod, 2007, 70(4):589
[28] HOULT DI, CHEN CN, EDEN H, et al. Elimination of baseline artifacts in spectra and their integrals[J].J Magn Reson, 1983, 51(1):110
