门冬氨酸鸟氨酸原料药生物安全性检查标准方法的研究  

Study on the standard method for biological safety inspection of L-ornithine L-aspartate active pharmaceutical ingredients

作　　者：林昊 郑美玲 张赞 黄逯 莫玉焕 谢鹏 吴超权 高红伟 LIN Hao;ZHENG Meiling;ZHANG Zan;HUANG Lu;MO Yuhuan;XIE Peng;WU Chaoquan;GAo Hongwei(Guangxi University of Chinese Medicine,Nanning,Guangxi,530200 P.R.China;Guangxi Institute for Drug Control,Nanning,Guangxi,530021 P.R.China)

机构地区：[1]广西中医药大学,广西南宁530200 [2]广西壮族自治区药品检验研究院,广西南宁530021

出　　处：《华西药学杂志》2024年第4期407-410,共4页West China Journal of Pharmaceutical Sciences

基　　金：广西壮族自治区药品监督管理局药品安全性科研项目(桂药监科2021-04直属)。

摘　　要：目的建立门冬氨酸鸟氨酸原料药的生物安全性检验标准方法。方法根据2020年版《中国药典》中通则方法进行异常毒性、降压物质、升压物质的生物安全性检验标准研究,设定检查限值,对3批门冬氨酸鸟氨酸原料药进行相关项目的检查验证。结果3批门冬氨酸鸟氨酸原料药样品的半数致死量可信限下限的1/4分别为754.7、752.0、747.7mg·kg^(-1),按25mL·kg^(-1)来设置,门冬氨酸鸟氨酸的试验浓度限值为30mg·mL^(-1);3批原料药给药333、267mg·kg^(-1)时,均未超过0.1μg·kg^(-1)磷酸组胺对照品所致降压水平的1/2,符合结果判定规定的反应值范围,建议设定上限267mg·kg^(-1)为门冬氨酸鸟氨酸降压物质检查的限值;67mg·kg^(-1)给药剂量所致的反应值均小于0.45IU·kg^(-1)对照品,约为1/2,建议将临床用药剂量的1/5即67mg·kg^(-1)作为升压物质检查的上限值。3批原料药生物安全性检查的结果均符合规定。结论所用方法可用于门冬氨酸鸟氨酸原料药异常毒性、降压物质和升压物质的检查。OBJECTIVE To establish a standard method for biosafety test of L-ornithine L-aspartate active pharmaceutical ingredients(OAAPI).METHODS According to the General rules of Chinese Pharmacopoeia(2020 edition),three biosafety tests including abnormal toxicity,vasopressor substance and depressor substance were conducted,and the limits were set.Related items were checked and verified for three batches of OAAPI.RESULTS 1/4 of the lower LDso confidence limits of the three batches of 0AAPI were 754.7 mg·kg^(-1),752.0 mg·kg^(-1)and 747.7 mg·kg^(-1),respectively.Consequently the limit was set as 30 mg·mL^(-1)in the abnormal toxicity test according to 25 mg·kg^(-1).Antihypertensive level caused by three batches of OAAPI at the doses of 333 mg·kg^(-1)and 267 mg·kg^(-1)did not exceed 1/2 of that caused by 0.1μg.kg^(-1)of histamine phosphate,which was in line with the specified range.Consequently 267 mg mL^(-1)was recommended as the limit in the test of depressor substance.The vasopressor value caused by three batches of OAAPI at the doses of 67 mg·kg^(-1)was all smaller than those caused by standard(0.45 IU·kg^(-1)),and nearly half of those caused by standard(0.45 IU·kg^(-1)).Consequently 67 mg·kg^(-1),which was 1/5 of the clinical dose of L-ornithine L-aspartate,was recommended as the limit in the test of vasopressor substance.According to this standard,three batches of OAAPI in these biosafety tests all met the requirements.CONCLUSION The method can be used for the detection of abnormal toxicity,vasopressor substance and depressor substance of OAAPI.

关 键 词：门冬氨酸鸟氨酸 生物安全性 异常毒性 降压物质 升压物质 原料药 

分 类 号：R917[医药卫生—药物分析学]