“…At present, several methods have been proposed including labeling and label-free analytical techniques. Labeling analysis techniques, such as fluorescence − and radionuclide labeling, , can trace the biodistribution of LNPs in vivo , but are faced with the limitations of inaccuracy, unsafety, and high cost . As a label-free method, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a safe and reliable strategy, which has highly sensitive analysis. , However, it is devastating for the lipid membrane of LNPs when organic reagents are used in the pretreatment of biological samples, which makes it hard to identify drug-loading LNPs. , To date, how to accurately recognize and then sensitively detect intact LNPs (i-LNPs) has hit a breaking point.…”