泰万菌素兽用国家标准品的研制

doi:10.11843/j.issn.0366-6964.2020.08.023

摘要/Abstract

摘要： 旨在研制首批泰万菌素兽用国家标准品，用于酒石酸泰万菌素及其制剂中泰万菌素的效价测定。采用精制后的泰万菌素酒石酸盐为原料进行本批泰万菌素标准品的研制，原料分装后按照酒石酸泰万菌素质量标准及《中华人民共和国兽药典》2015年版中的规定对其进行质量检测及均匀性评价，采用紫外-可见分光光度法测定最大吸收波长，60℃减压干燥法测定干燥失重，高效液相色谱法测定泰万菌素A组分，并以原始发明厂的标准品为基准，采用抗生素微生物检定法中三剂量管碟法进行协作标定，对标定结果进行合并计算，作为本批标准品的效价赋值。结果显示，分装后的标准品经60℃减压干燥至恒重后减失重量为2.0%，均匀性评价符合要求，在289 nm的波长处有最大吸收，抗生素微生物检定法测定的泰万菌素效价为822 U·mg^-1。本研究研制的首批泰万菌素兽用国家标准品各项检测指标均符合规定，可作为国家标准品发放，用于酒石酸泰万菌素原料及制剂中泰万菌素的效价测定，便于生产企业和质量检定部门进行酒石酸泰万菌素原料及制剂的质量控制，对于提高和保证兽药质量具有重要意义。

关键词: 泰万菌素, 国家标准品, 抗生素微生物检定法, 效价

Abstract: This experiment was conducted to prepare the first batch of national standard of tylvalosin to determine the potency of tylvalosin in tylvalosin tartrate and its preparations. The refined tylvalosin tartrate was used as raw material. After dispersal of the raw materials, the quality inspection and uniformity evaluation were tested according to the requirements of quality standard and Chinese Veterinary Pharmacopoeia 2015 edition. Ultraviolet spectrophotometry was applied to determine the maximum absorption wavelength. Vacuum drying at 60 ℃ was applied to determine the loss on drying. HPLC was applied to determine the tylvalosin A. Based on the standard products of the original invention factory, the three dose tube dish method in antibiotic microbiological assay was used for collaborative calibration. The results showed that the weight loss was 2.0%, the uniformity evaluation was in accordance with the regulations, the maximum absorption wavelength was 289 nm, the potency value was 822 U·mg^-1. The prepared national standard of tylvalosin met all the relevant requirements. It is convenient for production enterprises and quality inspection departments to control the quality of tylvalosin tartrate and its preparations, and it is of great significance to improve and ensure the quality of veterinary drugs.

Key words: tylvalosin, national standard, antibiotic microbiological assay, potency

中图分类号:

S859.79

戴青, 杨秀玉, 韩宁宁, 王轩, 赵晖. 泰万菌素兽用国家标准品的研制[J]. 畜牧兽医学报, 2020, 51(8): 1985-1992.

DAI Qing, YANG Xiuyu, HAN Ningning, WANG Xuan, ZHAO Hui. Preparation of National Standard of Tylvalosin for Veterinary Use[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(8): 1985-1992.

参考文献 27

[1]	冯言言, 田伟. 大环内酯类药物泰万菌素的研究进展[J]. 广东畜牧兽医科技, 2015, 40(6):5-6, 12.FENG Y Y, TIAN W. Research progress of macrolide tylvalosin[J]. Guangdong Journal of Animal and Veterinary Science, 2015, 40(6):5-6, 12. (in Chinese)
[2]	韩冰, 张荣飞, 晨光, 等. 泰万菌素对断奶仔猪生产性能的影响[J]. 黑龙江畜牧兽医, 2017(9):197-198.HAN B, ZHANG R F, CHEN G, et al. Effect of tylvalosin on the growth performance of weaning piglet[J]. Heilongjiang Animal Science and Veterinary Medicine, 2017(9):197-198. (in Chinese)
[3]	MOGES R, DE LAMACHE D D, SAJEDY S, 等. 泰万菌素的抗炎效果分析[J]. 文丽, 李仕超, 译. 猪业科学, 2018, 35(12):24-28.MOGES R, DE LAMACHE D D, SAJEDY S, et al. Analysis of anti-inflammatory effect of tylvalosin[J]. WEN L, LI S C, trans. Swine Industry Science, 2018, 35(12):24-28. (in Chinese)
[4]	朱晓娟, 王华丽, 齐鹏, 等. 酒石酸乙酰异戊酰泰乐菌素在猪体内的药代动力学研究[J]. 中国兽医杂志, 2013, 49(2):73-75.ZHU X J, WANG H L, QI P, et al. Pharmacokinetics of aivlosin in pigs[J]. Chinese Journal of Veterinary Medicine, 2013, 49(2):73-75. (in Chinese)
[5]	MANCHESTER A C, WEBB C B, BLAKE A B, et al. Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs[J]. J Vet Int Med, 2019, 33(6):2605-2617.
[6]	PALLARÉS F J, LASA C, ROOZEN M, et al. Use of tylvalosin in the control of porcine enzootic pneumonia[J]. Vet Record Open, 2015, 2(1):e000079.
[7]	GARMYN A, VEREECKEN M, DE GUSSEM K, et al. Efficacy of tylosin and tilmicosin against experimental Mycoplasma gallisepticum infection in chickens[J]. Avian Dis, 2019, 63(2):359-365.
[8]	TAVÍO M M, POVEDA C, ASSUNÇÃO P, et al. In vitro activity of tylvalosin against Spanish field strains of Mycoplasma hyopneumoniae[J]. Vet Record, 2014, 175(21):539.
[9]	ZHU H J, WANG W H, LIU J H, et al. Immobilization of Streptomyces thermotolerans 11432 on polyurethane foam to improve production of acetylisovaleryltylosin[J]. J Ind Microbiol Biotechnol, 2015, 42(1):105-111.
[10]	KUHNERT P, OVERESCH G. Molecular epidemiology of Mycoplasma hyopneumoniae from outbreaks of enzootic pneumonia in domestic pig and the role of wild boar[J]. Vet Microbiol, 2014, 174(1-2):261-266.
[11]	吴剑平, 张婧, 李丹妮, 等. 分散固相萃取法结合液相色谱串联质谱法检测鸡可食性组织中泰万菌素及3-乙酰泰乐菌素残留量[J]. 中国兽药杂志, 2017, 51(8):30-39.WU J P, ZHANG J, LI D N, et al. Determination of aivlosin and 3-acetyl tylosin in edible chicken tissues by dispersive solid phase extraction combined with liquid chromatography-tandem mass spectrometry[J]. Chinese Journal of Veterinary Drug, 2017, 51(8):30-39. (in Chinese)
[12]	张文刚, 姜芹, 孙冰清, 等. 抗生素微生物检定法测定酒石酸泰万菌素预混剂含量的不确定度分析[J]. 上海畜牧兽医通讯, 2018(2):5-7.ZHANG W G, JIANG Q, SUN B Q, et al. Analysis of uncertainty in the determination of tylvalosin tartrate premix by antibiotic microbiological assay[J]. Shanghai Journal of Animal Husbandry and Veterinary Medicine, 2018(2):5-7. (in Chinese)
[13]	吴家鑫, 尚飞, 张国栋, 等. UPLC-Q-TPF-MS测定酒石酸泰万菌素可溶性粉中的泰万菌素[J]. 中国兽医杂志, 2016, 52(9):108-110.WU J X, SHANG F, ZHANG G D, et al. Determination of tylvalosin in tylvalosin tartrate soluble powder by UPLC-Q-TPF-MS[J]. Chinese Journal of Veterinary Medicine, 2016, 52(9):108-110. (in Chinese)
[14]	中国兽药典委员会. 兽药质量标准2017年版化学药品卷[M]. 北京:中国农业出版社, 2017.Chinese Veterinary Pharmacopoeia Commission. Veterinary drug quality standard 2017 chemical volume[M]. Beijing:China Agriculture Press, 2017. (in Chinese)
[15]	张秀英, 陆连寿, 李翠, 等. 我国兽药标准物质供应现状分析与建议[J]. 中国兽药杂志, 2015, 49(1):57-59.ZHANG X Y, LU L S, LI C, et al. Analysis of supply status for veterinary durg reference standards[J]. Chinese Journal of Veterinary Drug, 2015, 49(1):57-59. (in Chinese)
[16]	王小慈, 张秀英, 李翠, 等. 美国化学药品标准物质管理情况概述及分析[J]. 中国兽药杂志, 2018, 52(10):16-21.WANG X C, ZHANG X Y, LI C, et al. USA chemical reference standard materials' management overview and analysis[J]. Chinese Journal of Veterinary Drug, 2018, 52(10):16-21. (in Chinese)
[17]	中国兽药典委员会. 中华人民共和国兽药典2015年版一部[M]. 北京:中国农业出版社, 2016.Chinese Veterinary Pharmacopoeia Commission. People's republic of China veterinary pharmacopoeia 2015 PartⅠ[M]. Beijing:China Agriculture Press, 2016. (in Chinese)
[18]	胡昌勤. 2015年版《中国药典》有关抗生素的增修订及其质量控制方向[J]. 中国药学杂志, 2015, 50(20):1764-1769.HU C Q. Revision of specifications of antibiotic in the Chinese Pharmacopoeia 2015 and the trend of antibiotic quality control[J]. Chinese Pharmaceutical Journal, 2015, 50(20):1764-1769. (in Chinese)
[19]	陈桂良, 徐新元, 王依婷, 等. 新药开发研究过程中药品标准物质的标定[J]. 上海计量测试, 2002, 29(2):18-20.CHEN G L, XU X Y, WANG Y T, et al. The determination of pharmaceutical reference materials during new drug development and research[J]. Shanghai Measurement and Testing, 2002, 29(2):18-20. (in Chinese)
[20]	胡昌勤, 成双红. 抗生素生物标准品的确定[J]. 中国药事, 2001, 15(4):263-265, 266.HU C Q, CHENG S H. Determination of biological reference standards of antibiotics[J]. Chinese Pharmaceutical Affairs, 2001, 15(4):263-265, 266. (in Chinese)
[21]	杨淑先, 崔春英, 刘英, 等. 协作标定首批国家标准品吉他霉素[J]. 中国药师, 2005, 8(2):170.YANG S X, CUI C Y, LIU Y, et al. Cooperate to calibrate the first batch of national standard kitasamycin[J]. China Pharmacist, 2005, 8(2):170. (in Chinese)
[22]	崔春英, 杨淑先. 国家标准品克拉霉素的协作标定[J]. 临床医学, 2002, 22(10):43.CUI C Y, YANG S X. Collaborative calibration of clarithromycin[J]. Clinical Medicine, 2002, 22(10):43. (in Chinese)
[23]	陈亚飞, 肖新月, 何平, 等. 标准物质稳定性考察规范解读和有效期管理方式的研究[J]. 中国药事, 2018, 32(3):317-322.CHEN Y F, XIAO X Y, HE P, et al. Interpretation of reference material stability investigation requirements and study on expiry date management methods[J]. Chinese Pharmaceutical Affairs, 2018, 32(3):317-322. (in Chinese)
[24]	戴青, 韩宁宁, 赵晖, 等. 苄星氯唑西林国家对照品的研制[J]. 中国兽药杂志, 2019, 53(7):18-24.DAI Q, HAN N N, ZHAO H, et al. Development of benzathine cloxacillin as national reference[J]. Chinese Journal of Veterinary Drug, 2019, 53(7):18-24. (in Chinese)
[25]	CASTRO L, MOREIRA E G, VASCONCELLOS M B A, et al. Stability assessment of a bovine kidney reference-material candidate[J]. J Radioanal Nucl Chem, 2018, 317(2):1133-1139.
[26]	马秋平, 王箐舟, 侯继锋, 等. 人免疫球蛋白甲型肝炎抗体国家标准品的研制[J]. 药物分析杂志, 2018, 38(2):303-306.MA Q P, WANG Q Z, HOU J F, et al. Preparation of national standard for anti-hepatitis A immunoglobulin[J]. Chinese Journal of Pharmaceutical Analysis, 2018, 38(2):303-306. (in Chinese)
[27]	刘莉莎, 邓利娟, 任雪, 等. 首批矛头蝮蛇血凝酶国家标准品及对照品的研制[J]. 中国药事, 2019, 33(12):1456-1463.LIU L S, DENG L J, REN X, et al. Development of the first batch of national reference material and the control material for hemocoagulase bothrops atrox[J]. Chinese Pharmaceutical Affairs, 2019, 33(12):1456-1463. (in Chinese)