Comparative tissue distribution analysis of Achyranthes bidentata Blume saponins via intragastric, intraperitoneal, and intravenous administration using simultaneous UPLC-MS/MS detection

Saponins, the primary bioactive components of Achyranthes bidentata Blume (AB), exhibit neuroprotective and anti-inflammatory properties. However, the lack of pharmacokinetic (PK) data, particularly on tissue distribution and first-pass effects, critically hinders their therapeutic development. Therefore, a rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method (9-min run time) was validated to simultaneously quantify five AB saponins in mice tissues (brain, heart, liver, spleen, lung, kidney; n = 5 per time point) at 10, 30, 60, 120, 240 min post-administration. The method demonstrated excellent linearity (R² > 0.99, 1–2500 ng/mL), precision (RSD ≤ 7.04 %), accuracy (85%–115 %), and recovery rates (86.6%–97.2 %, RSD ≤ 11.39 %) per ICH M10 guidelines. The results demonstrate that the saponin concentrations in various tissues after IG and IP administration were lower compared to those after IV administration, with levels reaching only 10 % of the latter. Although all these compounds are pentacyclic triterpenoid saponins with an oleanane skeleton, their tissue distribution in vivo varies significantly. The elimination of achyranthoside D, ginsenoside R0, and araloside A is relatively slow in various tissues. In contrast, chikusetsusaponin IVa is rapidly eliminated from various tissues. The ability of four saponins to cross the blood-brain barrier is highly beneficial for the development of therapeutic drugs for central nervous system diseases. Additionally, the results from different administration routes indicate that AB saponins may exhibit a pronounced gastrointestinal and hepatic first-pass effect in vivo, which should be considered in future research. This study can guide multi-route study of AB saponins provides critical insights for formulation optimization and dosing regimen design to mitigate first-pass effects