布洛芬注射液微量元素与中性硼硅玻璃安瓿相容性研究

Compatibility Between Trace Elements in Ibuprofen Injection and Neutral Borosilicate Glass Ampoules

目的 考察布洛芬注射液中微量元素与中性硼硅玻璃安瓿的相容性。方法 通过加速试验[温度(40±2)℃,相对湿度(90±10)%,时间3个月]模拟布洛芬注射液的存放条件,制备样品,采用电感耦合等离子体质谱(ICP-MS)法测定布洛芬注射液中微量元素的含量,通过在线内标的方式消除基质效应和干扰,测量模式为KED模式,等离子体射频功率为1 550 W,等离子气流速为15.0 L/min,载气流速为1.02 L/min,泵速为40 r/min,进样延迟时间为30 s,氧化物为CeO^(+)/Ce^(+)<2%,双电荷为Ce^(++)/Ce^(+)<2%。结果 钾(K)、镁(Mg)、铝(Al)、铁(Fe)、钠(Na)的质量浓度在50~2 000 ng/mL范围内,硼(B)、铬(Cr)、锰(Mn)、锌(Zn)、砷(As)、镉(Cd)、锑(Sb)、钡(Ba)、铅(Pb)的质量浓度在1.0~100.0 ng/mL范围内与仪器信号强度线性关系良好(r≥0.999 0,n=6);检测限分别为1.00~3.00 ng/mL、0.009~0.251 ng/mL,定量限分别为2.00~9.00 ng/mL、0.025~0.837 ng/mL;精密度和重复性试验结果的RSD均低于2.5%(n=6);平均加样回收率为82.47%~115.07%,RSD为1.23%~3.71%(n=9)。5批样品中均未检出Mg,Cd,Sb,Pb,其余元素的浸出量均低于规定限值。结论 所建立的方法可用于考察布洛芬注射液中微量元素与中性硼硅玻璃安瓿的相容性。

Objective To investigate the compatibility between trace elements in Ibuprofen Injection and neutral borosilicate glass ampoules.Methods The storage conditions of Ibuprofen Injection were simulated by the accelerated test[at the temperature of(40±2)℃,at the relative humidity of(90±10)%,for three months],the samples were prepared,and the contents of trace elements in Ibuprofen Injection were determined by the inductively coupled plasma-mass spectrometry(ICP-MS),with the online internal standard to eliminate matrix effect and interference.The measurement mode was KED mode,the plasma radio frequency power was 1550 W,the plasma gas flow rate was 15.0 L/min,the carrier gas flow rate was 1.02 L/min,the pump rate was 40 r/min,the injection delay time was 30 s,the oxide was CeO^(+)/Ce^(+)<2%,and the double charge was Ce^(^(++))/Ce^(^(+))<2%.Results The linear range of potassium(K),magnesium(Mg),aluminum(Al),iron(Fe)and sodium(Na)was 50-2000 ng/mL,while that of boron(B),chromium(Cr),manganese(Mn),zinc(Zn),arsenic(As),cadmium(Cd),antimony(Sb),barium(Ba)and lead(Pb)was 1.0-100.0 ng/mL(r≥0.9990,n=6).The limit of detection(LOD)of K,Mg,Al,Fe and Na was in the range of 1.00-3.00 ng/mL,while that of B,Cr,Mn,Zn,As,Cd,Sb,Ba and Pb was in the range of 0.009-0.251 ng/mL.The limit of quantitation(LOQ)of K,Mg,Al,Fe and Na was in the range of 2.00-9.00 ng/mL,while that of B,Cr,Mn,Zn,As,Cd,Sb,Ba and Pb was in the range of 0.025-0.837 ng/mL.The RSDs of precision and repeatability tests were lower than 2.5%(n=6).The average recovery of the above trace elements was in the range of 82.47%-115.07%,and the RSD was in the range of 1.23%-3.71%(n=9).Mg,Cd,Sb or Pb was not detected in the five batches of samples,and the leaching amount of other elements was lower than the specified limit.Conclusion The established method can be used to investigate the compatibility between trace elements in Ibuprofen Injection and neutral borosilicate glass ampoules.