Currently the pharmacokinetic (PK) research of herbal medicines is still limited and facing critical technical challenges on quantitative analysis of multi-components from biological matrices which often accompanied by lacking of authentic standards and low concentration. This present work contributes to the development of an integrated strategy for extensive pharmacokinetics assessments, and a selective and sensitive method independent of authentic standards for multi-components analysis based on the use of ultra-performance liquid chromatography/quadrupole-time-of-flight/MS (UPLC-TOF-MS) and UPLC-TOF-MRM (rnhanced target). Initially, phytochemicals were identified by UPLC-TOF-MS analysis, subsequently the identified components were matched with authentic standards and pre-classified, and UPLC-QTOF-MRM method optimized and developed. To guarantee reliable results, three rules are necessary: (1) detection with a mass error of less than 5ppm; (2) same class chemical compositions with structural high similarity between analytes with and without authentic reference substance; (3) a matching retention time between TOF-MRM mode and TOF-MS within 0.2min. The developed and validated method was applied for the simultaneous determination of 12 lignans in rat plasma after administered with wine processed Schisandra Chinensis fructus (WPSCF) extract. Such an approach was found capable of providing extensive pharmacokinetic profiles of multi-components absorbed into blood after oral administrated with WPSCF extract. The results also indicated that significant difference in pharmacokinetics parameters of dibenzocyclooctadiene lignans was observed between schizandrin and gomisin compounds. For lignans, the absorption via gastrointestinal tract were all rapid and maintained relatively long retention time, especially for schisantherin A and schisantherin B with higher plasma exposure.
Phenylethanoid glycosides are the bioactive components in Monochasma savatieri that primarily contains savaside A, acteoside, and isoacteoside. Pharmacological research has been comprehensive, but there have been few studies on pharmacokinetics, especially about savaside A. An ultra high performance liquid chromatography with tandem mass spectrometry with multiple reaction monitoring mode was developed and validated for the simultaneous determination of the three compounds from M. savatieri. Meanwhile, this method was fully validated and successfully applied to compare the pharmacokinetics and bioavailability following four different routes included intravenous injection, intraperitoneal injection, muscle injection, and oral administration. The results indicated that the three compounds could be rapidly absorbed within 1 h, and the main pharmacokinetic parameters showed significant differences (P < 0.05). The bioavailability of oral administration, intramuscular injection, and intraperitoneal injection did not exceed 0.2, 25, and 10%, respectively. Comparing the bioavailability, it exhibited that acteoside > isoacteoside > savaside A following the four administration routes. Notably, the isomerization position of acteoside and isoacteoside mainly occurred in the liver according to the pharmacokinetics profiles of intraperitoneal and intravenous injection, in addition, isoacteoside exhibited more structural selectivity than acteoside in vivo. It demonstrated that three compounds undergo different processes, mainly affected by the first‐pass effect and their intestinal stability is extremely poor.
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