定量核磁共振氟谱法测定盐酸莫西沙星及其3种杂质对照品的含量

Determination of reference standards of moxifloxacin hydrochloride and its three impurities by quantitative fluorine nuclear magnetic resonance

摘要

目的: 建立盐酸莫西沙星及其3种杂质对照品含量测定的定量核磁共振氟谱法。方法: 使用Bruker Avance NEO 600 MHz核磁共振波谱仪,以4,4′-二氟二苯甲酮为内标物,氘代二甲基亚砜(DMSO-d₆)为溶剂,zgig脉冲程序,32次采样(NS),采样时间为2.88 s,弛豫延迟时间(D1)为10 s,采集盐酸莫西沙星及其3种杂质(盐酸莫西沙星杂质Ⅰ、杂质Ⅲ、杂质Ⅳ)对照品的核磁共振氟谱并进行定量分析。结果: 盐酸莫西沙星及其3种杂质对照品的定量峰与内标物4,4′-二氟二苯甲酮的定量峰在核磁共振氟谱上分离度良好,盐酸莫西沙星、杂质Ⅰ、杂质Ⅲ、杂质Ⅳ分别在2.988~14.70、3.012~15.17、3.149~15.26、2.857~14.58 mg·mL^－1范围内线性关系良好(r＞0.999 4),测定精密度和重复性良好。定量核磁共振氟谱法与质量平衡法测定的含量结果基本一致。结论: 本文建立的盐酸莫西沙星及其3种杂质对照品含量测定的定量核磁共振氟谱法简便、快捷、准确性高,为对照品的建立及含量测定提供了参考。

Abstract

Objective: To establish a quantitative fluorine nuclear magnetic resonance (qFNMR) method for the determination the content of reference standards of moxifloxacin hydrochloride and its three impurities. Methods: The fluorine nuclear magnetic resonance spectra of the reference standards of moxifloxacin hydrochloride and its three impurities (Impurity Ⅰ, Impurity Ⅲ, and Impurity Ⅳ) were collected using a Bruker Avance NEO 600 MHz spectrometer with 4,4′-difluorobenzophenone as the internal standard and DMSO-d₆ as the solvent. The spectra were acquired with the zgig pulse program, 32 scans (NS), an acquisition time of 2.88 s, and a relaxation delay time (D1) of 10 s, and quantitative analysis was performed. Results: The quantitative peaks of moxifloxacin hydrochloride and its three impurities were well separated from that of the internal standard 4,4′-difluorobenzophenone on the fluorine NMR spectra. Good linear relationships were obtained for moxifloxacin hydrochloride, Impurity Ⅰ, Impurity Ⅲ and Impurity Ⅳ in the ranges of 2.988~14.70, 3.012~15.17, 3.149~15.26, 2.857~14.58 mg·mL^－1, respectively (r>0.999 4). The precision and repeatability of the method were good. The content results determined by the qFNMR method were basically consistent with those obtained from the mass balance method. Conclusion: The established qFNMR method for the content determination of reference standards of moxifloxacin hydrochloride and its three impurities is simple, rapid, and highly accurate, thus providing a reference for the establishment and content determination of these reference standards.

关键词

盐酸莫西沙星 / 杂质 / 对照品 / 含量测定 / 定量核磁共振氟谱法 / 质量平衡法

Key words

moxifloxacin hydrochloride / impurities / reference standards / content determination / quantitative fluorine nuclear magnetic resonance / mass balance method

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基金资助

中国食品药品检定研究院中青年发展研究基金资助项目(2025C10)