瑞芬太尼是一类新型、 理想、 手术中常用的一种麻醉镇痛药, 具有起效迅速、 半衰期短、 易于控制、 术后苏醒快等优点, 进入人体后以肾脏代谢为主, 经脱脂代谢后, 形成羧酸代谢物, 即瑞芬太尼酸, 因此对瑞芬太尼及其代谢物瑞芬太尼酸的结构研究很有必要。 目前文献只有对原型药物的结构研究, 而其代谢物瑞芬太尼酸的结构研究未见报道。 建立了紫外吸收光谱法、 红外吸收光谱法、 核磁共振波谱法(包含1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC和DEPT)以及质谱方法对瑞芬太尼酸的结构信息进行了鉴别研究。 其中紫外吸收光谱显示瑞芬太尼酸的芳香结构和共轭体系信息, 在紫外末端附近与254.0 nm附近有最大吸收, 分别与该物质E2和B带相对应, 说明分子中存在苯环特征结构。 采用溴化钾压片法制备瑞芬太尼酸样品, 进行红外光谱测试, 红外吸收光谱显示各个官能团的特征吸收峰, 均与瑞芬太尼酸结构中的主要官能团相一致。 利用NMR波谱法(包含1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC和DEPT)对瑞芬太尼酸所有的1H NMR和13C NMR信号进行了全面归属。 通过正离子检测模式进行质谱分析, 检测到质荷比(m/z)为362.98, 331.02, 303.10和259.09等碎片离子峰, 此检测结果与瑞芬太尼酸的分子量相一致, 且与瑞芬太尼酸的结构特征相对应。 结合光谱法等多种谱学技术可有效解析瑞芬太尼酸的波谱学数据, 并确证其结构。 结果表明: 多种谱学数据显示与瑞芬太尼酸的结构相一致, 可用于瑞芬太尼酸的结构研究, 并为其质量及纯度研究提供参考。

Remifentanil is a new, ideal, narcotic analgesic commonly used in surgery, which has the advantages of rapid effect, short half-life, easy to control, quick recovery after the operation etc. After entering the human body, remifentanil is mainly metabolized by the kidneys. Then remifentanil acid is formed after de-esterification metabolism. Therefore, it is necessary to study the structure of remifentanil and its metabolite remifentanic acid. At present, only the structure of the prototype drug has been studied, but the structure of its metabolite remifentanic acid has not been reported. Methods For the first time, this study established ultraviolet spectra, infrared spectra, nuclear magnetic resonance (NMR) spectra (i. e., 1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC and DEPT) and mass spectra for the chemical structure identification of remifentanil acid. The ultraviolet spectrum showed the aromatic structure and the information of the conjugated system of remifentanil acid. The maximum absorption in the vicinity of the ultraviolet end and 254.0 nm respectively corresponded to the E2 and B bands of the substance, which showed the presence of the benzene ring characteristic structure in the molecule. The infrared spectrum test was performed by preparing the remifentanil acid samples by the potassium bromide tablet method. The infrared spectrum was used to analyze the peaks of the functional group vibrations of remifentanil acid. All the 1H NMR and 13C NMR chemical shift signals of the compound were assigned rationally by NMR spectroscopy (including 1H NMR, 13C NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC and DEPT). Mass spectra were performed by positive electrospray ionization, and the mass-to-charge ratio (m/z) was 362.98, 331.02, 303.10, 259.09 and so on, which was consistent with the molecular weight of remifentanil acid and corresponding to the structural characteristics of remifentanil acid. The results showed that the above analytical data of a variety of spectral techniques coincided with the structure of remifentanil acid. Spectral analytical data is shown to be consistent with the structure of remifentanil acid, which can be used in the study of the structure of remifentanil acid and provide a reference for the study of its quality and purity.