注射用益气复脉(冻干)与氯化丁基胶塞相容性研究中棕榈酸和硬脂酸的含量测定

Determination of palmitic acid and stearic acidon study compatibility of Chlorinatedbutyl rubber plug andYiqi Fumai Lyophilized Injection

目的建立注射用益气复脉(冻干)(YQFM)中氯化丁基橡胶塞用棕榈酸和硬脂酸的含量测定方法,并对其稳定性进行考察。方法采用HP-5MS(30mm×0.25mm,0.25μm)气相色谱柱,柱温程序为初始温度150℃,5℃/min升至190℃保持2 min,5℃/min升至240℃保持10 min,体积流量1.8 mL/min,进样口250℃,检测器250℃,分流比1.0。进行专属性、线性关系、加样回收率、精密度、稳定性、耐用性方法学考察。选取6批YQFM(对应2个厂家的胶塞)倒立放置于下述环境进行试验,加速条件:温度(40±2)℃、相对湿度(75±5)%,长期条件:温度(25±2)℃、相对湿度(60±5)%,分别对0时,加速1、2、3、6个月及长期3、6、9、12、18、24、36个月各6批制剂中棕榈酸和硬脂酸含量进行测定。结果棕榈酸和硬脂酸专属性良好,在各自浓度范围内线性关系良好(r>0.999),检出限和定量限分别为0.1μg/mL和1.0μg/mL,加样回收率分别为93.92%、106.20%,稳定性、精密度及耐用性结果均符合要求。在加速及长期试验中,6批YQFM中棕榈酸和硬脂酸的含量与0时相比基本相当或略有增加,没有明显的变化,均远小于限度值。结论所建立的GC法准确可靠,可用于YQFM中棕榈酸和硬脂酸的含量测定;药品随着时间放置,棕榈酸和硬脂酸含量远低于安全限值,对产品质量不会造成安全风险。

Objective To establish a method for the content determination of palmitic acid and stearic acid in butyl rubber plug of YiqiFumai Lyophilized Injection and to investigate the stability ofsamples.Methods Using HP-5MS(30 mm×0.25 mm,0.25μm)gas chromatography column,the column initial temperature was 150℃,5℃/min rose to 190℃for two min,then 5℃/min rose to 240℃for 10 min,the volume flow rate was 1.8 mL/min,the inlet temperature was 250℃,the detector temperature was 250℃and the split ratio was 1.0.Results The linear relationship of palmitic acid and stearic acid were good in their own ranges(r>0.999).The average recovery of palmitic acid and stearic acid was 93.32%and 106.20%respectively.The precision and durability results are in line with the requirements;the content of palmitic acid and stearic acid in the study on the stability of YiqiFumai Lyophilized Injection sample was below the limit.Specificity,linear relationship,sample recovery,precision,stability and durability were investigated.Six batches of YQFM(corresponding to rubber plugs from two manufacturers)were selected and placed upside down in the following environment for test.Acceleration conditions were temperature(40±2)℃,relative humidity(75±5)%,and longterm conditions were temperature(25±2)℃and relative humidity(60±5)%.The contents of palmitic acid and stearic acid in 6 batches of preparation at 0,1,2,3,6 months of acceleration conditions and 3,6,9,12,18,24,36 months of long-term conditions were determined respectively.Conclusion The established method was accurate and reliable and can be used for the determination of palmitic acid and stearic acid in YiqiFumai Lyophilized injection.The content of palmitic acid and stearic acid is far below the safety limit as the drug is placed over time,which does not pose a safety risk to the product quality.