18F-FDG异常肝脏显像药物质谱测定及失控原因分析

目的探讨2-氟18-β-D-脱氧葡萄糖(18F-FDG)异常肝脏显像的原因及质量控制中的隐藏问题。方法应用GC/MS和MS/MS质谱分析并根据分析结果制备模拟样品;用TLC、HPLC进行质量控制;使用C18和Amino色谱柱并改变放射性探测器样品池体积分析模拟样品的放射化学纯度。隔日复查异常肝脏显像情况。结果GC/MS分析,结合NIST谱库检索,鉴定出药物中含有相对分子质量为376的化合物,名称为氨基聚醚K2.2.2(AminopolyetherK2.2.2);MS/MS分析,基峰为415.1,其次为377.2;模拟样品TLC分析见两个放射性峰,点样板碘显色可见接近原点处出现棕色斑点;HPLC分析模拟样品,因色谱柱和放射性探测器样品池体积的不同而结果不同;隔日PET/CT复查患者异常肝脏显像,肝脏高代谢消失。结论异常肝脏显像药物经质谱测定发现含有过量的K2.2.2,建议在药物放行前常规检测K2.2.2含量。

Mass spectrometric detection of abnormal liver imaging of the 18F-FDG injection and analysis of the causes in quality control

Objective To discuss the causes of abnormal liver uptake imaging of 18F-FDG injection and find out the problems in radiopharmaceutical quality control.Methods GC/MS and MS/MS were adopted in drug analysis,and simulation samples were prepared with considerations of the analysis results.TLC and HPLC methods were used for quality control.The column of C18 and amino was used,and the sample cell volume of radioactivity detector was changed to analyze the radioactive chemical purity of the simulation samples.Abnormal liver uptake imaging was checked the next day.Results GC/MS analysis combined with NIST database searching found that there was a chemical compound named K2.2.2 with a molecular weight of 376.MS/MS analysis indicated a base peak of 415.1 followed by 377.2.TLC analysis of the simulation samples found two radioactivity peaks.Iodine color test of the TLC SG plate showed brown spots near the origin.HPLC analysis found that the results differed with the difference in column and cell volume of the radioactivity detector.PET/CT scan of the abnormal liver imaging patients found that high uptake of liver disappeared the next day.Conclusion Abnormal liver uptake imaging was due to the existence of excessive K2.2.2 in the radiopharmaceutical product.It is suggested that routine determination of K2.2.2 concentration must be performed before release of the radiopharmaceutical product.