Abstract：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.
Key words：Remifentanil acid; Ultraviolet spectra; Infrared spectroscopy; Nuclear magnetic resonance; Assignment; Mass spectrometry; Structure identification
[1] WANG Qiang, BAO Fang, LIU Li-jun, et al（王 强, 鲍 方, 刘礼军, 等）. Journal of Clinical Anesthesiology(临床麻醉学杂志), 2014, 30(12): 1156.
[2] WANG Wei, YANG Wan-jie（王 伟, 杨万杰）. Journal of Clinical Anesthesiology(临床麻醉学杂志), 2015, 31(9): 926.
[3] CHEN Ren-jun, SHEN Xue-yong, NI Hui, et al（陈仁军, 沈学用, 倪 辉, 等）. Chinese Journal of General Surgery(中国普通外科杂志), 2018, 27(8): 1041.
[4] ZHOU Shao-dan, LU Hong-wen, MIAO Li-yan, et al（周少丹, 卢红文, 缪丽燕, 等）. West China Journal of Pharmaceutical Sciences(华西药学杂志), 2009, 24(2): 201.
[5] BI Xiao-ling, YOU Qi-dong, LI Yu-yan, et al（毕小玲, 尤启冬, 李玉艳, 等）. Chinese Journal o f Medicinal Chemistry(中国药物化学杂志), 2002, 12(6): 354.
[6] CUI Wen-tao, CHEN Zheng-wei, LI Guo-zheng（崔文涛, 陈政伟, 李国政）. Chinese Journal of Clinical Pharmacologys(中国临床药理学杂志), 2017, 33(11): 1029.
[7] PAN Zhen-guo, DONG Yun-jie, WANG Ming-yi（潘振国, 董云洁, 王明义）. Chinese Journal of Cancer Prevention and Treatment(中华肿瘤防治杂志), 2016, 23(S1): 168.
[8] MA Chun-hua, CAO Jun-han, YANG Zheng, et al（马春华, 曹俊涵, 杨 争, 等）. Chinese Journal of Antibiotics(中国抗生素杂志), 2014, 39(5): S3.
[9] YANG Zheng, RONG Xiao-juan, CAO Jun-han, et al（杨 争, 戎晓娟, 曹俊涵, 等）. China Measurement & Test(中国测试), 2014, 40(4): 56.
[10] BI Xiao-ling, YOU Qi-dong, CHEN Li（毕小玲, 尤启冬, 陈 莉）. Progress in Pharmaceutical Sciences(药学进展), 2003, 27(6): 360.
