定量核磁共振氢谱法测定4种盐酸莫西沙星杂质对照品的含量

Determination of Reference Standards of Four Moxifloxacin Hydrochloride Impurities by Quantitative Proton Nuclear Magnetic Resonance

目的建立测定4种盐酸莫西沙星杂质A、B、C、D对照品含量的定量核磁共振氢谱法(quantitative proton nuclear magnetic resonance,qHNMR)。方法采用核磁共振波谱仪采集4种盐酸莫西沙星杂质对照品的一维定量氢谱(^(1)H-NMR),以1,3,5-三甲氧基苯作为内标物,氘代二甲亚砜(DMSO-d6)或氘代氯仿(CDCl_(3))作为溶剂,脉冲程序为noesyigld1d,扫描次数(NS)为32次,弛豫延迟时间(D1)为30 s,测试温度为25℃,对4种盐酸莫西沙星杂质对照品进行定量研究。结果4种盐酸莫西沙星杂质对照品定量峰和1,3,5-三甲氧基苯定量峰信号在核磁共振氢谱上分离度良好,在线性范围内线性关系良好(r^(2)>0.9994),进样精密度和重复性良好。qHNMR法测定含量结果与质量平衡法测定含量结果基本一致。结论建立的qHNMR法准确可靠、简便快速,为该类杂质含量测定提供了新的方法,也可作为该类化学对照品采用质量平衡法定值结果的验证方法。

OBJECTIVE To establish a quantitative proton nuclear magnetic resonance(qHNMR)method for determination of the reference standards of moxifloxacin hydrochloride impurities A,B,C and D.METHODS Proton nuclear magnetic resonance(1H-NMR)spectra of four reference standards of impurities were obtained in dimethylsulfoxide-d6(DMSO-d6)or chloroform-d(CDCl_(3))using a nuclear magnetic resonance spectrometer.The internal standard was 1,3,5-trimethoxybenzene.All^(1)H-NMR spectra for quantitative analysis were measured with noesyigld1d pulse sequence using the following experimental parameters:32 number of scans(NS),relaxation delay time(D1)of 30 s,25℃testing temperature.RESULTS The quantitative peak signals of four moxifloxacin hydrochloride impurities and 1,3,5-trimethoxybenzene were well separated on 1H-NMR spectra,and the linear relationship was good within the linear range(r^(2)>0.9994).The injection precision and repeatability of the method were good.The contents of four reference standards of impurities determined by qHNMR method were basically consistent with those determined by mass balance method.CONCLUSION The established qHNMR method is accurate,reliable,simple,fast,which provides a new way for content determination of these impurities and can also be used as a mutual verification method for the calibration results of these reference substance by the mass balance method.