摘要
目的考察注射用益气复脉(冻干)(YQFM)与17种临床常用注射剂的配伍稳定性,为临床合理用药提供参考。方法模拟临床应用,以0.9%的氯化钠溶液为溶媒,按比例分别将YQFM与17种注射剂混合,考察配伍溶液在0、3、6、9、12 h内外观、p H值、不溶性微粒、紫外光谱的变化;采用HPLC测定YQFM中主要成分(人参皂苷Rg1、Re、Rb1、Rc、Rb2、Rd和五味子醇甲)的含量变化。结果 YQFM与注射用辅酶A、注射用盐酸纳洛酮配伍后,配伍液中粒径≥10μm、≥25μm的微粒数超出《中国药典》2015年版规定范围;与注射用环磷酰胺配伍后,配伍液中粒径≥10μm的微粒数超出规定范围,且各时间点色谱图与0 h相比,相似度均小于0.9;与维生素C注射液配伍后p H值变化明显(RSD=2.12%),相似度均小于0.9;与维生素B6注射液配伍后p H变化明显(RSD=3.00%),紫外全波段扫描图谱在340 nm附近发生显著变化,相似度均小于0.9;与奥扎格雷钠注射液配伍后,相似度均小于0.9;与氨茶碱注射液配伍后紫外全波段扫描图谱在340nm附近发生显著变化,相似度均小于0.9;与呋塞米注射液配伍后p H变化明显(RSD=3.64%),紫外全波段扫描图谱在340nm附近发生显著变化,相似度均小于0.9;与注射用泮托拉唑钠配伍后,溶液颜色变暗,出现絮状漂浮物,溶液中粒径≥10μm、≥25μm的微粒数均超出规定范围;与其他注射剂配伍后各项指标无显著变化,均符合相关规定。结论 YQFM与注射用辅酶A、注射用环磷酰胺、维生素C注射液、维生素B6注射液、奥扎格雷钠注射液、氨茶碱注射液、呋塞米注射液、注射用盐酸纳洛酮、注射用泮托拉唑钠配伍后理化性质发生变化,不可配伍使用;与维生素K1注射液、三磷酸腺苷二钠注射液、去乙酰毛花苷注射液、胞磷胆碱钠注射液、碳酸氢钠注射液、硝酸甘油注射液、地塞米松磷酸钠注射液、地西泮注射液配伍后理化性质无显著变化,需进一步考察其在体内相互作用情况。
Objective To investigate the compatibility stability of Yiqi Fumai Lyophilized Injection（YQFM） combined with 17 common injections to guide rational drug use. Methods The appearance, p H, insoluble particles and UV absorption spectrum of the compatible solution were observed and determined; the content changes of main compounds including ginsenosides Rg1, Re, Rb1,Rc, Rb2, Rd and schisandrin in YQFM were determined by HPLC at 0, 3, 6, 9, 12 h after mixing. Results After mixed with Coenzyme A for Injection（CAI）, Naloxone Hydrochloride For Injection（NHI）, the number of particles ≥ 10 and ≥ 25 μm exceeded the scope of Chinese Pharmacopoeia; after mixed with Cyclophosphamide for Injection（CI）, the number of particles ≥10μm exceeded the scope of Chinese Pharmacopoeia, the similarity of fingerprint was lower than 0.9; after mixed with Vitamin C Injection（VCI）, the obvious change was found in p H values（RSD = 2.12%）, the similarity of fingerprint was lower than 0.9; after mixed with Vitamin B6 Injection（VB6 I）, the obvious change was found in p H values（RSD = 3.00%）, UV absorption spectrum changed significantly at 340 nm, the similarity of fingerprint was lower than 0.9; after mixed with Sodium Ozagrel for Injection（SOI）, the similarity of fingerprint was lower than 0.9; after mixed with Aminophylline Injection（AI）, UV absorption spectrum changed significantly at 340 nm, the similarity of fingerprint was lower than 0.9; after mixed with Furosemide Injection（FI）, the obvious change was found in p H values（RSD = 3.64%）, UV absorption spectrum changed significantly at 340 nm; the similarity of fingerprint was lower than 0.9; after mixed with Pantoprazole Sodium for Injection（PSI）, the obvious change was found in the color at 9 h; the number of particles ≥10 and ≥25 μm exceeded the scope of Chinese Pharmacopoeia. Conclusion After mixed with CAI, NHI, CI, VCI, VB6 I, SOI, AI, FI and PSI, the physical and chemical properties change, and cannot be used together. After mixed with Vitamin K1 Injection（VK1 I）, Adenosine Disodium Triphosphate for Injection（ADTI）, Deslanoside Injection（DSI）,Sodium Bicarbonate Injection（SBI）, Citicoline Sodium Injection（CSI）, Nitroglycerin Injection（NI）, Dexamethasone Sodium Phosphate Injection（DSPI） and Diazepam Injection（DI）, the obvious change was not found, further examination need to be carried out.
作者
鞠爱春
褚延斌
陈晓宇
周学谦
苏小琴
李德坤
周大铮
余伯阳
JU Aichun;CHU Yanbin;CHEN Xiaoyu;ZHOU Xueqian;SU Xiaoqin;LI Dekun;ZHOU Dazheng;YU Boyang(Tianjin Tasly Pride Pharmaceutical Co., Ltd., Tianjin 300402, China;China Pharmaceutical University, Nanjing 210009, China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections, Tianjin 300402, China)
出处
《药物评价研究》
CAS
2018年第3期429-438,共10页
Drug Evaluation Research
基金
"重大新药创制"科技重大专项(2013ZX09402202)
