小儿消积止咳口服液及药用复合膜中12种常见抗氧剂的提取与迁移研究

Extraction and Migration Study of 12 Common Antioxidants in the Medicinal Composite Film of Pediatric Antitussive Oral Liquid for Children

建立了测定小儿消积止咳口服液及其包装材料(口服液体药用复合膜)中12种常见抗氧剂的超高效液相色谱-串联质谱(UPLC-MS/MS)法。采用Shim-pack GIST C18(100 mm×2.1 mm,2μm)为色谱柱,甲醇(含0.01 mol/L甲酸与甲酸铵)和水(含0.01 mol/L甲酸与甲酸铵)为流动相梯度洗脱;采用电喷雾离子源(ESI),以多反应监测(MRM)正离子模式进行定性定量分析。结果显示,12种抗氧剂在10~400 ng/mL范围内线性良好,相关系数(r)不小于0.9963,提取与迁移实验的检出限分别为0.40~13.25 ng/g和1.01~33.13 ng/mL,定量下限分别为1.35~44.17 ng/g和3.37~110.42 ng/mL,回收率为80.1%~114%,相对标准偏差(RSD,n=3)为1.5%~7.2%。药液中检出抗氧剂1010和168,但含量低于其每日允许最大暴露量(PDE),对药品安全性风险影响较小。该方法高效灵敏、准确可靠、操作简便,可用于小儿消积止咳口服液及其包装材料中12种常见抗氧剂的测定。

An ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed for the determination of 12 common antioxidants in pediatric antitussive oral liquid and its packaging material(oral liquid medicinal composite film).The chromatographic column used was Shim-pack GIST C18(100 mm×2.1 mm,2μm),with methanol(containing 0.01 mol/L formic acid and ammonium formate)and water(containing 0.01 mol/L formic acid and ammonium formate)as the mobile phase by gradient elution.Electrospray ionization(ESI)and multiple reaction monitoring(MRM)in positive ion mode were employed for qualitative and quantitative analysis.The results showed good linearity for the 12 antioxidants in the concentration ranges of 10 ng/mL to 400 ng/mL,with correlation coefficients(r)not less than 0.9963.The detection limits of extraction and migration were in ranges of 0.40-13.25 ng/g and 1.01-33.13 ng/mL,and the quantitative limits were in ranges of 1.35-44.17 ng/g and 3.37-110.42 ng/mL,respectively.The recoveries ranged from 80.1%to 114%,and the relative standard deviations(RSDs,n=3)were between 1.5%and 7.2%.Migration of antioxidants 1010 and 168 was detected in the medicinal solution,but their levels were below their respective permitted daily exposure(PDE),posing minimal impact on the safety risk of the medication.The method is highly efficient,sensitive,accurate,reliable,and easy to operate,making it suitable for the determination of 12 common antioxidants in pediatric antitussive oral liquid and its packaging material.