贮藏温度对注射用特利加压素关键质量属性影响分析&#x0002A;

王培; 鲁鑫; 马冰; 段玺玉; 覃婷婷; 韩晓捷; 白海娇

doi:10.16155/j.0254-1793.2024-1064

药物分析杂志 >

2025 , Vol. 45 >Issue 5: 907 - 914

DOI: https://doi.org/10.16155/j.0254-1793.2024-1064

标准研讨

贮藏温度对注射用特利加压素关键质量属性影响分析^*

王培 ,
鲁鑫 ,
马冰 ,
段玺玉 ,
覃婷婷 ,
韩晓捷 ,
白海娇

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天津市药品检验研究院,天津 300070

第一作者 Tel：（022）23374073;E-mail：ritaw_81@163.com

** 鲁鑫 Tel：（022）23374073;E-mail：luxin_boom@126.com;
白海娇 Tel：（022）23374073;E-mail：bhjdx@163.com

网络出版日期: 2025-10-13

基金资助

* 2023年国家药品抽检项目（国药监药管﹝2023﹞2号）

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Analysis of the impact of storage temperature on the critical quality attributes of terlipressin for injection^*

WANG Pei ,
LU Xin ,
MA Bing ,
DUAN Xi-yu ,
QIN Ting-ting ,
HAN Xiao-jie ,
BAI Hai-jiao

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Tianjin Institute of Drug Control, Tianjin 300070, China

Online published: 2025-10-13

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摘要

目的: 欧洲药典“Room temperature”与《中华人民共和国药典》“室温”概念不同,贮藏温度与长期稳定性试验设计、说明书撰写密切相关,本文探讨贮藏温度差异对注射用特利加压素关键质量属性的影响,以期引起仿制药企业对此问题的关注。方法: 基于不同厂家说明书贮藏温度不一致的问题,追溯原研药长期稳定性试验及贮藏温度,采用经过验证的有关物质和聚合物检查方法评价温度差异对产品关键质量属性的影响。结果: 放置于30 ℃的样品,有关物质增长幅度显著高于放置于15 ℃的样品。一家企业的样品于30 ℃放置仅5个月,聚合物就已超限。企业分歧源自部分企业忽视中欧药典差异,将原研药说明书“Room temperature”简单直译为“室温”。结论: 贮藏温度对注射用特利加压素的有关物质和聚合物影响显著,应将说明书中贮藏温度要求收窄至“不超过25 ℃”。

关键词： 中欧药典室温差异; 贮藏温度; 有关物质; 聚合物; 特利加压素

本文引用格式

王培 , 鲁鑫 , 马冰 , 段玺玉 , 覃婷婷 , 韩晓捷 , 白海娇 . 贮藏温度对注射用特利加压素关键质量属性影响分析^*[J]. 药物分析杂志, 2025 , 45(5) : 907 -914 . DOI: 10.16155/j.0254-1793.2024-1064

Abstract

Objective: To clarify the differences between the “Room temperature” definitions in the European Pharmacopoeia and the Chinese Pharmacopoeia, to emphasize that storage temperature was closely related to the design of long-term stability studies and product labeling, and to investigate the effects of storage temperature variations on the critical quality attributes (CQAs) of terlipressin for injection, so as to raise awareness among generic drug manufacturers regarding this critical issue. Methods: Given the discrepancies in storage temperature recommendations across different manufacturers’ product inserts, the original drug’s long-term stability studies and storage conditions were traced. Validated methods for related substances and polymer content were employed to assess the impact of temperature differences on the product’s CQAs. Results: Samples stored at 30 ℃exhibited a significantly higher increase in related substances compared to those stored at 15 ℃. In one manufacturer’s product, polymer levels exceeded specification limits within just five months of storage at 30 ℃. The divergence among manufacturers stems from some companies misinterpreting the original drug’s labeling by directly translating without considering the differences between Chinese and European Pharmacopoeias. Conclusion: Storage temperature has a significant impact on the levels of related substances and polymer content in terlipressin for injection. To ensure product quality, the storage temperature in the labeling should be restricted to “not exceeding 25 ℃.”

Key words： differences in “Room temperature” between Chinese and European Pharmacopoeias;; storage temperature; related substances; polymers; terlipressin

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