注射用二丁酰环磷腺苷钙与转化糖电解质注射液的配伍稳定性及辅助用药管理对策研究

Compatibility stability of calcium dibutyryladenosine cyclophosph-ate in multiple electrolytic and invert sugar injection and management strategies of adjuvant drugs

目的探讨注射用二丁酰环磷腺苷钙在转化糖电解质注射液中的稳定性及辅助用药管理。方法配制对照品溶液、供试品溶液、配伍溶液。按照《中国药典》(2015年版)的要求检查注射用二丁酰环磷腺苷钙与转化糖电解质注射液配伍溶液的颜色、澄清度、pH、不溶性微粒,采用高效液相色谱法检测配伍溶液中的药物相对百分含量。结果二丁酰环磷腺苷钙的峰形良好,保留时间为5.6min。二丁酰环磷腺苷钙在5.62~500.00μg/mL质量浓度的线性关系良好,定量限为5.62μg/mL,检测限为2.81μg/mL。二丁酰环磷腺苷钙的相对标准偏差(RSD)为0.36%,该分析方法的重复性良好。低、中、高浓度各样品在室温下放置0、1、2、4、6、12h和1、2、3、4、5、6d稳定,回收率分别为(101.3±0.89)%、(98.6±1.06)%、(99.2±0.91)%。0、1、2、4、6、12、24h后,配伍溶液Ⅰ~Ⅴ均为无色澄清液体、pH值均无明显变化。配伍溶液Ⅲ~Ⅴ的不溶性微粒符合药典的规定,Ⅰ、Ⅱ≥10μm不溶性微粒数量超出药典的规定。配伍溶液Ⅰ~Ⅴ中的二丁酰环磷腺苷钙相对百分含量符合药典要求。结论注射用二丁酰环磷腺苷钙的使用应严格掌握其适应证,并只能使用说明书规定的溶媒。

Objective To investigate the compatibility stability of calcium dibutyryladenosine cyclophosph-ate in multiple electrolytic and invert sugar injection and the management of hospital adjuvant drugs.Methods Preparation of reference solution,sample solution and compatibility solution.According to the requirements of the Chinese Pharmacopoeia(2015 Edition),the color,clarity,pH value and insoluble particles of compatibility solution with calcium dibutyryladenosine cyclophosph-ate and multiple electrolytic and invert sugar injection were examined.Results The spike of calcium dibutyryladenosine cyclophosph-ate was good,the retention time was 5.6 min.Calcium dibutyryladenosine cyclophosph-ate had a good linear relationship at the concentration of 5.62-500.00μg/mL.The limit of quantification was 5.62μg/mL and the detection limit was 2.81μg/mL.The relative standard deviation(RSD)of calcium dibutyryladenosine cyclophosph-ate was 0.36%.The method was reproducible.The samples with low,medium and high concentrations were stable at room temperature for 0,1,2,4,6,12 h and 1,2,3,4,5,6 d,the recoveries were(101.3±0.89)%,(98.6±1.06)%and(99.2±0.91)%respectively.After 0,1,2,4,6,12 and 24 h,theⅠ-Ⅴof the compatible solution was colorless clarified liquid,and the pH value had no obvious change.The insoluble particles of compatible solutionⅢ-Ⅴaccorded with the stipulation of Pharmacopoeia,and the number of insoluble particles ofⅠandⅡ≥10μm micron exceeded the stipulation of Pharmacopoeia.The relative percentage of the drugs in compatibility solutionsⅠ-Ⅴmet the requirements of pharmacopoeia.Conclusion The indication of calcium dibutyryladenosine cyclophosph-ate for injection should be strictly controlled and only the solvent prescribed in the instructions should be used.