定量核磁共振氢谱法测定枸橼酸托法替布片的有效含量  

Determination of Tofacitinib Citrate Tablets by Quantitative Proton Nuclear Magnetic Resonance

作　　者：刘慢 赵阗 刘会利 陈林[1] LIU Man;ZHAO Tian;LIU Hui-li;CHEN Lin(Henan Joint International Research Laboratory of Drug Discovery of Small Molecules,Henan Comprehensive Utilization of Edible and Medicinal Plant Resources Engineering Technology Research Center,Zhengzhou Key Laboratory of Synthetic Biology of Natural Products,Huanghe Science and Technology College,Zhengzhou 450063,China)

机构地区：[1]黄河科技学院河南省小分子新药研发国际联合实验室,河南省食药两用植物资源综合利用工程技术研究中心,郑州市天然产物合成生物学重点实验室,河南郑州450063

出　　处：《分析测试学报》2023年第3期363-367,共5页Journal of Instrumental Analysis

基　　金：河南省高等学校重点科研项目计划(22B360011);河南省科技攻关计划项目(222102310518)。

摘　　要：建立了枸橼酸托法替布片中有效含量的定量核磁共振氢谱测定方法。以托法替布化学位移δ7.13为定量峰,3,5-二甲基吡唑化学位移δ5.73为内标峰,氘代二甲亚砜(DMSO-D_(6))为溶剂,使用核磁共振谱仪采集混合物的氢谱,对枸橼酸托法替布片中的有效成分进行定量测定。该方法专一性强,在0.793~7.925 mg/mL范围内呈现良好的线性关系(r^(2)=0.9984)。精密度、重复性和稳定性的相对标准偏差(RSD)分别为0.82%、1.7%和0.67%。该方法测得的枸橼酸托法替布片中托法替布的质量分数为2.25%,其结果与高效液相色谱法基本一致。定量核磁共振氢谱法具有操作方便简单,可同时进行定性与定量,检测时间短,无需对照品等优势,可用于枸橼酸托法替布片有效含量的测定。A quantitative proton nuclear magnetic resonance(qHNMR)method was developed for determination on the effective content of tofacitinib citrate tablets,with dimethyl sulfoxide(DMSOD_(6))as the solvent and 3,5-dimethylpyrazole as the internal standard.Proton signal peaks of tofacitinib atδ7.13 andδ5.73 of 3,5-dimethylpyrazole were selected as the quantitative signals,respectively.The spectra of the mixture complex were collected under the conditions of pulse sequence zg30,relaxation delay time(D1)26 s,and scanning number(NS)16 times at 298 K on Bruker AvanceⅢ400 MHz NMR spectrometer.qHNMR method with high specificity showed a good linear relationship in the concentration range of 0.793-7.925 mg/mL,with linear correlation coefficient(r^(2))up to 0.9984.The relative standard deviation(RSD)of precision,repeatability and stability were 0.82%,1.7%and 0.67%,respectively.The content of tofacitinib in tofacitinib citrate tablets was determined to be 2.25%by qHNMR,which was basically consistent with the results by high performance liquid chromatography(HPLC).As a result,qHNMR method is an alternative way to determine the effective content of toacitinib cittrate tables.More importantly,it has many outstanding advantages,such as simple operation,short detection time,no requirement for reference standards,simultaneously qualitative and quantitative analysis.

关 键 词：定量核磁共振氢谱法 枸橼酸托法替布片 3 5-二甲基吡唑 含量测定 

分 类 号：O657.7[理学—分析化学] R917[理学—化学]