目的: 建立使用新型台式核磁共振仪测定替比夫定含量的方法。方法: 使用台式核磁共振仪,以1,4-二硝基苯为内标,氘代二甲亚砜为溶剂进行氢核磁共振定量测定,通过比较替比夫定样品响应信号与内标响应信号面积,计算替比夫定的含量,并进行方法学验证。结果: 替比夫定在10 ～120 mmol·L-1范围内线性关系良好,精密度RSD=1.2%(n=5),重复性RSD=0.35%(n=5)。氢核磁共振定量测定结果为99.0%,与质量平衡法结果(99.6%)基本一致。结论: 台式核磁共振仪体积小,容易操作,可以用于测定替比夫定的含量,加强药品质量控制。
Objective: To establish a method for the determination of telbivudine assay by benchtop nuclear magnetic spectrometer. Methods: The 1H quantitative nuclear magnetic resonance (1H-qNMR) spectrum was determined using 1,4-dinitrobenzene as the internal standard and deuterateddimethyl sulfoxide as the solvent on a benchtop nuclear magnetic spectrometer. The assay of telbivudine was calculated by comparing the response signal of sample and internal standard. Themethod validation was accomplished. Results: The linear regression of telbivudine in the range of 10-120 mmol·L-1 was good, the RSD of injection precision was 1.2% (n=5), and the reproducible RSD was 0.35% (n=5). The result from1H-qNMR was 99.0% and was consistent with the result from mass balance method (99.6%). Conclusion: Benchtop nuclear magnetic spectrometeris compact, easy to operate and maintain. It can be used to determine the assay of telbivudine and strength the quality control of chemical drugs.
[1] HOLZGRABE U. Quantitative NMR spectroscopy in pharmaceutical applications [J].Prog Nucl Magn Reson Spectrosc, 2010, 57(2):229
[2] LIU J, LIU Y, DAI Z, et al. Structural and quantitative analysis of three C-glycolsylflavones by variable temperature proton quantitative nuclear magnetic resonance [J/OL].J Anal Methods Chem, 2017, 4934309:1 [2017-01-23]. https://www.hindawi.com/journals/jamc/2017/4934309/
[3] WEBER M, HELLRIEGEL C, RUECK A. Using high-performance 1H NMR (HP-qNMR) for the certification of organic reference materials under accreditation guidelines-describing the overall process with focus on homogeneity and stability assessment [J].J Pharm Biomed Anal, 2014, 93:102
[4] 赵婧伊,左志辉.RP-HPLC法测定替比夫定片的有关物质及含量[J].天津科技,2018,45(2):31
ZHAO JY, ZUO ZH. RP-HPLC determination assay of telbivudine tablets and its related substances [J].Tianjin Sci Technol, 2018,45(2):31
[5] 林小燕,万红艳,陈敬华.紫外分光光度法测定替比夫定的含量[J].海峡药学,2009, 21(9):46
LIN XY, WAN HY, CHEN JH. Determination of telbivudine by UV spectrophotometry[J].Strait Pharm J, 2009, 21(9):46
[6] 中华人民共和国药典2020年版. 四部[S]. 2020:53
ChP 2020.Vol Ⅳ [S]. 2020:53
[7] USP 40-NF 35 [S]. 2020:629
[8] EP 9.0 [S]. 2020:54
[9] CHAE Y, MIN S, PARK E, et al. Real-time reaction monitoring with in operando flow NMR and FTIR spectroscopy:reaction mechanism of benzoxazole synthesis [J].Anal Chem, 2021, 93(4):2106
[10] DUCHOWNY A, ADAMS A. Compact NMR spectroscopy for low-cost identification and quantification of PVC plasticizers [J].Molecules, 2021, 26(5):1221
[11] CASTAING-CORDIER T, LADROUE V, BESACIER F, et al. High-field and benchtop NMR spectroscopy for the characterization of new psychoactive substances [J].Forenic Sci Int, 2021, 321:110718
[12] RIEGEL SD, LESKOWITZ GM. Benchtop NMR spectrometers in academic teaching [J].Trend Anal Chem, 2016, 83:27
[13] 许洁,陆志檬. 替比夫定治疗慢性乙型肝炎的进展[J].中华肝脏病杂志,2006,14(12):958
XU J, LU ZM. Progress in the treatment of chronic hepatitis B with telbivudine [J].Chin J Hepatol, 2006, 14(12):958
[14] HOLZGRABE U, DEUBNER R, SCHOLLMAYER C, et al. Quantitative NMR spectroscopy-applications in drug analysis[J].J Pharm Biomed Anal, 2005, 38(5):806
[15] PAULI GF, JAKI BU, LANKIN DC. Quantitative 1H NMR:development and potential of a method for natural products analysis[J].J Nat Prod, 2005, 68(1):133
