A pseudo-targeted pharmacokinetic study on traditional Chinese medicine formulae by the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry integrated with scheduled multiple reaction monitoring platform: QiangHuoShengShi decoction as a case.

QiangHuoShengShi decoction (QHSS), a classical prescription traditional Chinese medicine (TCMs), boasts a lengthy clinical history in treating various rheumatic diseases. No pharmacokinetic (PK) studies on QHSS were reported to date while its in vitro and in vivo chemical fingerprints were comprehensively reported. This study aims to reveal the time-dependent changes in the concentrations of multi-known and -unknown components in rats after oral administration of QHSS, thereby offering insights for further research into its pharmacodynamic mechanisms. The prediction of multiple reaction monitoring (MRM) parameters for known and unknown analytes was first achieved using a standards-independent ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method coupled with linear correlation analysis. Subsequently, specific parameters were then determined using single-factor optimization by the ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). Finally, the concentrations of known and unknown analytes in plasma biosamples were determined using a built scheduled multiple reaction monitoring (sMRM) method. The sMRM parameters for 90 compounds were predicted and optimized. The pharmacokinetic parameters, including mean time to reach peak concentration (Tmax), maximum plasma concentration (Cmax), area under concentration-time curve (AUC), mean resident time (MRT), were characterized for 32 measurable components (17 with standard substances and 15 without standard substances). The pharmacokinetic parameters of 28 components from biosamples of the rheumatoid arthritis (RA) group were further compared with those from the normal group, revealing significant differences (either increased or decreased) in their PK parameters. A pseudo-targeted pharmacokinetic study of QHSS was successfully conducted by a standards-independent UHPLC-Q-TOF-MS/MS with UHPLC-sMRM-MS/MS method, which holds significant promise for subsequent research into the medicinal substances of QHSS. It can also serve as a powerful tool for multi-compounds pharmacokinetic study of more TCMs.