醋酸奥曲肽原料及其制剂的杂质分析

发布时间：2018-05-18 15:20

本文选题：生长抑素类似物 + 多肽类药物　；参考：《药物分析杂志》2017年03期

【摘要】：目的:探讨醋酸奥曲肽原料及其制剂的杂质情况。方法:采用高效液相色谱法,色谱柱为Hypersil C_(18)(4.6 mm×250 mm,5μm),流动相A为四甲基氢氧化铵溶液(取10%四甲基氢氧化铵溶液20mL,加水880mL,用10%磷酸溶液调节p H至5.4)-乙腈(900∶100),流动相B为四甲基氢氧化铵溶液(取10%四甲基氢氧化铵溶液20mL,加水380mL,用10%磷酸溶液调节p H至5.4)-乙腈(400∶600),流速1.0mL·min~(-1),紫外检测波长为210 nm,分析醋酸奥曲肽原料及制剂的杂质谱,并比较了原料间、制剂间的杂质情况。再结合影响因素试验、加速试验、配伍稳定性试验,分析影响杂质产生的因素及杂质的变化情况,并确证未知杂质的结构。结果:醋酸奥曲肽杂质谱显示其主要杂质共21个,不同企业间的原料、制剂杂质谱均有差异,同一企业不同剂型的制剂杂质谱也有差异;影响因素试验及加速试验表明温度、湿度、光及贮藏均可增加醋酸奥曲肽的杂质;确定了5个未知杂质的结构,分别为杂质6(D-Thr~6-OCTR)、杂质7([des-Thr-ol~8]-OCTR)、杂质9(Des-Thr~6-OCTR)、杂质12(D-Cys~7-OCTR)、杂质13(Des-Lys~5-OCTR)及杂质15([AC-D-phe~1]-OCTR)。结论:醋酸奥曲肽的杂质主要来源于制剂的生产及贮藏过程,应进一步提高制剂的生产工艺及严格控制贮藏条件,以提高产品的质量。
[Abstract]:Objective: to study the impurity of octreotide acetate and its preparation. Methods: high performance liquid chromatography (HPLC) was used. The chromatographic column is Hypersil Che / 18mm 脳 250mm / m ~ (5 渭 m), the mobile phase A is tetramethylammonium hydroxide solution (20 mL) (10% tetramethylammonium hydroxide solution 20 mL, water 880 mL), the pH is adjusted to 5.4% acetonitrile 900: 100m with 10% phosphoric acid solution, and the mobile phase B is a tetramethylammonium hydroxide solution (10%). The mobile phase A is a tetramethylammonium hydroxide solution (10% tetramethylammonium hydroxide solution). Taking 10% tetramethylammonium hydroxide solution for 20 mL, adding water 380 mL, adjusting pH to 5.4% -acetonitrile 400: 600m with 10% phosphoric acid solution, flow rate 1.0mL minmin-1g, UV detection wavelength is 210nm, the impurity spectrum of raw material and preparation of octreotide acetate is analyzed. The impurity between raw materials and preparations was compared. Combined with influence factor test, acceleration test and compatibility stability test, the factors affecting impurity production and impurity change were analyzed, and the structure of unknown impurity was confirmed. Results: the impurity spectrum of octreotide acetate showed 21 major impurities. The impurity spectra of raw materials and preparations were different among different enterprises, and the impurity spectra of different formulations of the same enterprise were also different. The impurity of octreotide acetate can be increased by humidity, light and storage, and the structure of 5 unknown impurities are determined, which are impurity 6D-Thrr-6-OCTRN, impurity 7 ([des-Thr-ol~8] -OCTRN, impurity 9Des-Thrrttrium 6-OCTRN, impurity 12DD-Cys-7-OCTRR, impurity 13Des-Lys-Lys-5-OCTR) and impurity 15 ([AC-D-phe~1] -OCTRN). Conclusion: the impurity of octreotide acetate mainly comes from the production and storage process of the preparation. The production process and storage conditions of the preparation should be further improved in order to improve the quality of the product.
【作者单位】：河南省食品药品检验所;
【分类号】：R917

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