高效液相色谱法测定阿司匹林丁香酚酯咀嚼片的有关物质

doi:10.16431/j.cnki.1671-7236.2023.07.040

Abstract

Abstract: 【Objective】 The study was to determine the related substances of aspirin eugenol ester (AEE) chewable tablets by high performance liquid chromatography (HPLC), and establish a more convenient and accurate detection method for the quality control of AEE chewable tablets.【Method】 The specificity, linear range, limits of detection and quantification, precision, repeatability, stability, recovery, destructive testing, durability testing, and sample determination were investigated by HPLC, in order to comprehensively evaluate the determination method of related substances in AEE chewable tablets, and calculate the content of related substances by self-contrast method.The chromatographic separation was performed using a Phenomenex Luna C18 column (150 mm×4.6 mm, 5 μm) at 35 ℃.The mobile phase consisted of water containing 0.5% phosphoric acid (A) and acetonitrile (B) with gradient elution.The flow rate was 1.0 mL/min, the detection wavelength was 279 nm, and the injection volume was 10 μL.【Result】 The results showed that the HPLC method of AEE chewable tablets had high specificity, and the detected peaks were well separated from other peaks.The linear relation between peak area and concentration of the AEE was good in the range of 0.26-26.00 μg/mL, R²=1 (n=7).In addition, the linear relation between peak area and concentration of the impurity A was well in the range of 0.25-25.50 μg/mL, R²=0.9996 (n=7).The limits of quantification of AEE and impurity A were 0.52 and 0.51 μg/mL, and the limits of detection were 0.26 and 0.25 μg/mL, respectively.The relative standard deviation (RSD) of precision was less than 1%.RSD of intraday repeatability, daytime repeatability and stability were 0.88%, 2.50% and 1.84%, respectively.Average recovery was 100.14% (n=9, RSD=1.66%).Destructive test showed that material was basically conserved under different destruction conditions, and the material conservation was between 95% and 105%.The durability test showed that the durability of the detection conditions was good, RSD was 1.87%.In the three batches of samples, the content of impurity A in AEE chewable tablets was less than 0.5%, and the total impurity content was less than 1.0%.【Conclusion】 The method was validated to be simple, specific, accurate and suitable for the determination of related substances in AEE chewable tablets.

Key words: aspirin eugenol ester (AEE); chewable tablets; high performance liquid chromatography; related substances

CLC Number:

S859.79

BAI Lixia, LIU Xiwang, YANG Yajun, QIN Zhe, LI Shihong, GE Wenbo, LI Jianyong. Determination of Related Substances in Aspirin Eugenol Ester Chewable Tablets by High Performance Liquid Chromatography[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(7): 3007-3016.

References

[1] LI J Y, YU Y G, WANG Q W, et al.Synthesis of aspirin eugenol ester and its biological activity[J].Medicinal Chemistry Research, 2012, 21(7):995-999.
[2] 李剑勇, 张继瑜, 周绪正, 等.丁香酚阿斯匹林酯药用化合物及其制剂和制备方法[P].中国专利:CN101270052A, 2008-09-24. LI J Y, ZHANG J Y, ZHOU X Z, et al.Medicinal compound of eugenol aspirin ester and its preparation and preparation method[P].Chinese Patent:CN101270052A, 2008-09-24.(in Chinese)
[3] 贾希希, 李剑勇.新型非甾体抗炎药物阿司匹林丁香酚酯的研究进展[J].中国兽药杂志.2020, 54(10):69-75. JIA X X, LI J Y.Progress in the new nonsteroidal anti-inflammatory drug aspirin eugenol ester[J].Chinese Journal of Veterinary Drug, 2020, 54(10):69-75.(in Chinese)
[4] 叶得河, 于远光, 李剑勇, 等.阿司匹林丁香酚酯的高效解热作用及作用机制[J].中国药理学与毒理学杂志, 2011, 25(2):151-155. YE D H, YU Y G, LI J Y, et al.Antipyretic effects and its mechanisms of aspirin eugenol ester[J].Chinese Journal of Pharmacology and Toxicology, 2011, 25(2):151-155.(in Chinese)
[5] TAO Q, ZHANG Z D, QIN Z, et al.Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels[J]. Frontiers in Immunology, 2022, 13:939106.
[6] KARAM I, MA N, LIU X W, et al.Regulation effect of aspirin eugenol ester on blood lipids in Wistar rats with hyperlipidemia[J].BMC Veterinary Research, 2015, 11:217-223.
[7] KARAM I, MA N, LIU X W, et al.Lowering effects of aspirin eugenol ester on blood lipids in rats with high fat diet[J].Lipids in Health and Disease, 2016, 15(1):196-200.
[8] SHEN D S, YANG Y J, KONG X J, et al.Aspirin eugenol ester inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt1/CD40L pathways[J].European Journal of Pharmacology, 2019, 852:1-13.
[9] MA N, YANG G, LIU X, et al.Impact of aspirin eugenol ester on cyclooxygenase-1, cyclooxygenase-2, 1 C-reactive protein, prothrombin and arachidonate 5-lipoxygenase in healthy rats[J].Iranian Journal of Pharmaceutical Research, 2017, 16(4):1443-1451.
[10] ZHANG Z D, YANG Y J, LIU X W, et al.Aspirin eugenol ester ameliorates paraquat-induced oxidative damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway[J].Toxicology, 2021, 453:152721.
[11] ZHANG Z D, YANG Y J, LIU X W, et al.The protective effect of aspirin eugenol ester on oxidative stress to PC12 cells stimulated with H₂O₂ through regulating PI3K/Akt signal pathway[J].Oxidative Medicine and Cellular Longevity, 2021, 2021:5527475.
[12] 赵晓乐.阿司匹林丁香酚酯对大鼠的急性毒性、慢性毒性和一代繁殖毒性研究[D].北京:中国农业科学院, 2017. ZHAO X L.Studies on acute toxicity, chronic toxicity, F1 reproductive and developmental toxicity of aspirin eugenol ester in rats[D].Beijing:Chinese Academy of Agricultural Sciences, 2017.(in Chinese)
[13] 中国兽药典委员会.中华人民共和国兽药典[M].北京:中国农业出版社, 2020. CHINESE VETERINARY PHARMACOPOEIA COMMITTEE.Veterinary Pharmacopoeia of the People's Republic of China[M].Beijing:China Agriculture Press, 2020.(in Chinese)
[14] 朱春媚, 滕健皓, 张梦, 等.咀嚼片质量评价方法研究进展[J].中国新药杂志, 2022, 31(7):645-654. ZHU C M, TENG J H, ZHANG M, et al.Research progress on quality evaluation methods of chewable tablets[J].Chinese Journal of New Drugs, 2022, 31(7):645-654.(in Chinese)
[15] 孙秉喆, 邢嘉萌, 严真, 等.咀嚼片的研发要点及研究进展[J].中南药学, 2022, 20(10):2373-2378. SUN B Z, XING J M, YAN Z, et al.Key points in development and research progress in chewing tablets[J].Central South Pharmacy, 2022, 20(10):2373-2378.(in Chinese)
[16] 焦钰婷.阿司匹林丁香酚酯咀嚼片的制备及质量控制[D].兰州:甘肃农业大学, 2019. JIAO Y T.Preparation and quality control of aspirin eugenol ester chewable tablets[D].Lanzhou:Gansu Agricultural University, 2019.(in Chinese)
[17] 农业部兽药评审中心.兽药研究技术指导原则汇编[M].北京:化学工业出版社, 2012. VETERINARY DRUG EVALUATION CENTER OF MINISTRY OF AGRICULTURE.Compilation of Technical Guidelines for Research on Veterinary Drug[M].Beijing:Chemical Industry Press, 2012.(in Chinese)
[18] 焦钰婷, 焦增华, 刘希望, 等.HPLC法测定阿司匹林丁香酚酯在咀嚼片中的含量[J].动物医学进展, 2019, 40(10):48-53. JIAO Y T, JIAO Z H, LIU X W, et al.Content determination of aspirin eugenol ester chewable tablets by HPLC[J].Progress in Veterinary Medicine, 2019, 40(10):48-53.(in Chinese)
[19] 农业部兽药评审中心.化学药物制剂研究基本技术指导原则[M].北京:化学工业出版社, 2005. VETERINARY DRUG EVALUATION CENTER OF MINISTRY OF AGRICULTURE.Basic Technical Guiding Principles for the Research of Chemical Pharmaceutical Preparations[M]. Beijing:Chemical Industry Press, 2005.(in Chinese)
[20] 李晓婷, 白玉彬, 李冰, 等.基于HPLC法测定五氯柳胺阿苯达唑复方混悬液中的有关物质[J].中国畜牧兽医, 2019, 46(11):3422-3431. LI X T, BAI Y B, LI B, et al.Determination of related substances in oxyclozanide and albendazole coupound suspension by HPLC[J].China Animal Husbandry & Veterinary Medicine, 2019, 46(11):3422-3431.(in Chinese)
[21] 耿响, 刘希望, 杨亚军, 等.乙酰氨基阿维菌素缓释注射剂中乙酰氨基阿维菌素含量与有关物质HPLC检测方法的建立[J].中国畜牧兽医, 2021, 48(12):4681-4689. GENG X, LIU X W, YANG Y J, et al.Establishment of HPLC method for determination of eprinomectin and related substances in eprinomectin sustained-release injection[J].China Animal Husbandry & Veterinary Medicine, 2021, 48(12):4681-4689.(in Chinese)
[22] 焦增华, 刘希望, 杨亚军, 等.HPLC法测定阿司匹林丁香酚酯的研究[J].动物医学进展, 2020, 4(4):72-76. JIAO Z H, LIU X W, YANG Y J, et al.Determination of aspirin eugenol ester by HPLC[J].Progress in Veterinary Medicine, 2020, 4(4):72-76.(in Chinese)

Determination of Related Substances in Aspirin Eugenol Ester Chewable Tablets by High Performance Liquid Chromatography

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	ZHANG Le, ZHANG Guangfeng, ZHU Chongmiao, WU Zhi, ZHU Shanyuan, YU Shenglan, FENG Qi, XING Xiaoling, ZHAO Qiannan. Study on Pharmacokinetics of Cyclodextrin-encapsulated Flufenicol in Pigs [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(6): 1934-1941.
[2]	XU Xiangyue, MA Wenjin, AN Boyu, WANG Hanyu, CHENG Guyue, LIU Zhenli, HUANG Lingli. Detection of Doxycycline in Soil Using Solid Phase Extraction and High Performance Liquid Chromatography-Ultraviolet [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(12): 4174-4180.
[3]	JIAO Yuting, JIAO Zenghua, YANG Xiaopu, LI Jianyong. Mechanism of AEE in Preventing and Curing Canine Cardiovascular Diseases Based on Network Pharmacological Method [J]. , 2019, 46(4): 1191-1198.
[4]	LI Xiaoting, BAI Yubin, LI Bing, DONG Zhen, SUN Jichao, CHENG Fusheng, ZHANG Jiyu. Determination of Related Substances in Oxyclozanide and Albendazole Compound Suspension by HPLC [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3422-3431.
[5]	DENG Ruihan, LIN Bailiang, YANG Liu, LU Yanrong, PENG Jianbo, WU Wenjian, YANG Lei, HAO Zhihui, YANG Shanzhong, HE Jiakang. Thin Layer Chromatography Identification and Content Determination of Zhongjiefeng Sanqing Granule [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(10): 3095-3105.
[6]	LI Lei-ting, LIU Jun-hua, LIU Bao-tao, FU Hong-lei, ZOU Ming. Residue Analysis of Five Kinds of Penicillins in Eggs by High Performance Liquid Chromatography-Ultraviolet Detection [J]. , 2017, 44(8): 2483-2488.
[7]	WANG Si-han, ZHANG Ji-yu, XING Shou-ye, LI Bing, ZHOU Xu-zheng. Content Determination of Ivermectin in the Ivermectin Microemulsion Injection [J]. , 2017, 44(6): 1861-1868.
[8]	GUO Jie，ZHANG Chao-fei，GAO Geng-qu，MA Guang-hui，MA Wei. Research Progress on Determination of Residues of Antibiotic in Milk by High Performance Liquid Chromatography-tandem Mass Spectrometry [J]. , 2014, 41(1): 236-239.
[9]	ZHAO Qiu-lian, ZHANG Li-hong, ZHANG Qiu-mei, HUANG Xiao-lin, LIU De-xin, FU Xu-yang, LIANG Jie, E Lai-ming. Determination of Hydroxyproline in Raw Milk by Ultra High Performance Liquid Chromatography [J]. , 2013, 40(S1): 85-88.
[10]	GU Yu-feng, LIU Zhao-ying, ZHANG Ming-jun, ZHOU Si, HUANG Ya-jun, LI Yu-huan, WU Yong, SUN Zhi-liang. Determination of Dissolution Amount of Icariin in Different Particle Sizes of Epimedium by HPLC [J]. , 2013, 40(3): 224-226.
[11]	YANG Li-yun, LIU Cheng-mo, XIAO Jin-yong, HUANG Zhi-cheng, LI Juan. Determination of Seven Kinds of Biogenic Amines in Fishmeal by a High Performance Liquid Chromatography Method [J]. , 2013, 40(12): 112-115.
[12]	YAO Fang-fang, ZHU Ruo-cen, LIU Zhao-ying, TIAN Shi-jie, TANG Zhao-shan, LIU Qi, WU Yong. Determination of Sanguinarine in Rat Liver Microsomes Incubation System by HPLC [J]. , 2012, 39(12): 159-161.
[13]	XIE Kai-zhou;XU Dong;CHEN Shu-qin;XIE Xing;HUANG Yu-ping;JIA Long-fei;GUO Hui-sheng;WANG Jin-yu. Determination of Residues of Thiamphenicol in Chicken Muscle by HPLC with Fluorescence Detection [J]. , 2011, 38(3): 163-166.
[14]	YAO Yun-shan;SHEN Jian-zhong;WU Cong-ming;CHENG Lin-li. Determination of 3-methyl-quinoxaline-2-carboxylic Acid in Porcine Liver by High Performance Liquid Chromatography [J]. , 2011, 38(2): 187-190.
[15]	ZHOU De-gang;HE Cheng;SUN Zhi-wen;LI Ying-chao. Determination of p-coumaric Acid(PCA) in PCA Solution by RP-HPLC〖 [J]. , 2011, 38(2): 239-242.