[UHPLC-Orbitrap-MS and targeted metabolomics reveal chemical distribution characteristics and main chemical content of Tibetan medicine Liuwei Muxiang Pills].

This study aims to identify the main chemical components of the Tibetan medicine Liuwei Muxiang Pills(LWMXP) by using mass spectrometry and targeted metabolomics, analyze the distribution characteristics of its main components in the serum and tissue(stomach, small intestine, and liver), and assess their exposure levels in gastric cancer cells. Ultra-high-resolution mass spectrometry was employed to identify the chemical components in the extract of LWMXP, which were confirmed by matching with the standard database. Then, the same method was used to identify the migratory components in the blood, tissue, and gastric cancer cells of rats after oral administration of LWMXP. Targeted metabolomics of the multiple reaction monitoring(MRM) mode was employed to determine the content of the main components of LWMXP in the serum, tissue, and gastric cancer cells of rats treated with LWMXP. A total of 1 171 prototype compounds were identified from the extract of LWMXP, including 209 alkaloids, 267 terpenoids, 62 polyketones, 76 amino acids and short peptides, and 379 shikimic acid and phenylpropanoid acid compounds. Meanwhile, 51 prototype compounds were identified in the serum and tissue of rats after administration of LWMXP. Among them, 12 compounds-chlorogenic acid, costunolide, dihydroferuperine, ellagic acid, gallic acid, herculin, hydroprotopine, isoquercitrin, L-valine, piperlongumine, piperine, and protopine-showed distribution in both the serum and tissue. Targeted metabolomics was employed for quantitative analysis on 10 main components. The results showed that gallic acid, piperine, and protopine were all detected in the serum and tissue, while(+)-bicuculline and isoquercitrin were only detected in the gastric tissue. Costunolide presented high distribution in the stomach and small intestine, while ellagic acid was detected in the serum and gastric tissue. Gallic acid, corilagin, kaempferol, ellagic acid, and protopine were detected in gastric cancer cells. The findings provide a scientific basis for comprehensive analysis of the pharmacodynamic substance basis, quality standard improvement, and mechanism elucidation of LWMXP.