盐酸吉西他滨用于膀胱热灌注的药物稳定性研究  

Thermalstability study of gemcitabine hydrochloride used in hyperthermic intravesical chemotherapy

作　　者：张媚媚 李靖 庞廷媛 李佳 柳晓蕊 林蔚 方淑娴 曾丽斯 简晓顺 ZHANG Mei-mei;LI Jing;PANG Ting-yuan;LI Jia;LIU Xiao-rui;LIN Wei;FANG Shu-xian;ZENG Li-si;JIAN Xiao-shun(Department of Pharmacy,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China;Department of Urology,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China;Department of Gastrointestinal Surgery 2 Section,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China;Institute of Oncology,Affiliated Cancer Hospital&Institute of Guangzhou Medical University,Guangdong Guangzhou 510095,China)

机构地区：[1]广州医科大学附属肿瘤医院,药学部,广东广州510095 [2]广州医科大学附属肿瘤医院,泌尿外科,广东广州510095 [3]广州医科大学附属肿瘤医院,肿瘤胃肠二区,广东广州510095 [4]广州医科大学附属肿瘤医院,肿瘤研究所,广东广州510095

出　　处：《中国医院药学杂志》2022年第16期1673-1679,共7页Chinese Journal of Hospital Pharmacy

基　　金：广州市卫生和计划生育科技项目—一般引导项目(编号:20171A011318)。

摘　　要：目的:考察盐酸吉西他滨(gemcitabine hydrochloride,GEM)溶于0.9%氯化钠(normal saline,NS)或NS和人工尿液(artificial urine,AU)的混合溶液中,在不同浓度和温度下的稳定性,为GEM用于膀胱热灌注化疗提供热稳定性依据。方法:分别配制GEM 2 g和3 g,溶于NS或NS混合AU为溶媒的样品(简写为GEM 2 g+NS,GEM 2 g+NS+AU、GEM 3 g+NS,GEM 3 g+NS+AU),检测在室温(25℃)恒温6 h,37,43,45,47,50℃恒温2 h内热稳定性的变化。根据2020年版《中国药典》中的方法测定样品的pH、溶液性状和澄清度、可见异物、有关物质和GEM含量的变化。结果:GEM 2 g+NS,GEM 2 g+NS+AU、GEM 3 g+NS,GEM 3 g+NS+AU在室温(25℃)恒温6 h,37,43,45,47,50℃恒温2 h后,均为无色澄清溶液,pH维持在3.6,有关物质中胞嘧啶最大值为(0.0007±0.00008)%,α-异构体未检出,最大未知单杂最大值为(0.03±0.009)%,总杂最大值为(0.04±0.03)%,GEM相对含量在(98.85±0.75)%~(100.65±1.16)%(RSD≤1%)。结论:GEM在NS或NS混合AU为溶媒中,分别在室温(25℃)恒温6 h,37,43,45,47,50℃恒温2 h,稳定性良好,可用于膀胱热灌注化疗。OBJECTIVE To investigate the stability of Gemcitabine Hydrochloride(GEM)dissolved in 0.9%normal saline solution(NS)and NS mixed Artificial urine(AU)solution,at different concentrations and temperatures,so as to provide the basis for GEM applied in hyperthermia intravesical chemotherapy.METHODS We prepared the solution of test sample(short for GEM 2 g+NS,GEM 2 g+NS+AU,GEM 3 g+NS,GEM 3 g+NS+AU),separately.The temperatures were kept in room temperature(25℃)for 6 h,and 37,43,45,47,50℃for 2 h.The pH value,clarity test,visible particles,the related substances and contents of GEM were determined according to The Chinese Pharmacopoeia(version 2020).RESULTS The solution of GEM 2 g+,GEM 2 g+NS+AU,GEM 3 g+NS,GEM 3 g+NS+AU were all clear,colorless and transparent,the pH value was 3.6.The contents of GEM remained stable at 25℃for 6 h,and 37,43,45,47,50℃for 2 h,respectively.The related substances and contents of GEM were also stable,which the maximum value of cytosine was(0.0007±0.00008)%,α-isomer can't detected,the unknown single heterogeneous were less than(0.03±0.009)%,the total miscellaneous was less than(0.04±0.03)%,while the contents of GEM were between(98.85±0.75)%and(100.65±1.16)%(RSD≤1%).CONCLUSION GEM has good thermal stability in different concentrations,remained stable at 25℃for 6 h,and 37,43,45,47,50℃for 2 h,including in NS and AU,and can be an ideal selection used in hyperthermic intravesical chemotherapy of bladder cancer.

关 键 词：膀胱癌 盐酸吉西他滨 膀胱热灌注化疗 热稳定性 

分 类 号：R917[医药卫生—药物分析学]