Although wide applications towards ischemic stroke in clinic, the therapeutic materials of Longxuetongluo Capsule (LTC) that is composed of total phenolic extract of Chinese dragon's blood, are still largely unclear. Exposure pattern characterization of those drug-derived components in vivo, notably in circulation system has been recommended as a viable approach to disclose the effective components of a given herbal medicine. Herein, we aimed to develop a robust method being capable of multi-component quantification in either rat plasma or tissues following oral administration of LTC, and to clarify the kinetic profiles of 11 primary drug-derived phenolic derivatives. Proteins precipitation was carried out for the plasma as well as homogenized tissue samples with acetonitrile. Chromatographic separations were achieved using UHPLC equipped with a shim-pack XR-ODS II column, and confidence-enhanced detection was accomplished through the joint employment of selected-reaction monitoring and tandem mass spectrometry (SRM-MS/MS) on a hybrid triple quadrupole-linear ion trap mass spectrometer. Diverse validation assays proved the method to be sensitive, precise, and rapid for simultaneous determination of those 11 components. Pharmacokinetic and tissue distribution investigations were subsequently conducted in rat after a single 500 mg/kg oral dose. Rapid absorption (Tmax, 11.53-68.27 min) and elimination (T1/2, 6.893-57.90 min) occurred for all analytes-of-interest. Extensive occurrences were observed for 7,4'-dihydroxy-5-methoxyhomoisoflavanone (Cmax, 340.0 ng/mL), thevetiaflavone (Cmax, 42.86 ng/mL), 5,7,4'-trihydroxyhomoisoflavanone (Cmax, 41.55 ng/mL), and pterostilbene (Cmax, 25.49 ng/mL) in plasma. Significant distributions occurred for all analytes in the liver as well as kidney, and several compounds could be found in brain. The findings described are envisioned to provide promising information for the in-depth clarification of the therapeutic entities, and also to offer a practical approach for therapeutic drug monitoring of LTC in clinic.
Keywords: Longxuetongluo capsule; Pharmacokinetics; Phenolic compounds; Tissue distribution; UHPLC–SRM-MS/MS.
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