A fast and accurate method for the pharmacokinetic research of four coumarin analogs in Fructus cnidii using capillary electro‐chromatography with a methacrylate ester‐based monolithic column

Abstract

In the present study, a monolithic capillary column with higher permeability was developed for the in vivo discrimination of four coumarin analogs (bergapten, 2'-acetylangelicin, imperatorin, and osthole) that typically require long separation times in HPLC. Instead of conventional methacrylate ester monolith (containing 19.5% porogen) with insufficient permeability (K = 1.52 - 1.66 × 10 M ) for plasma sample, the proposed column (20.5% porogen) had better permeability (around 3.80 × 10 M ) while properties such as pore distribution, stability, and resolution changed slightly. As a result, due to the negatively charged electro-dynamic flow of the methacrylate ester groups in the monolith, the migration of targeted analytes was achieved within 6 min (compared with 30 min in HPLC) with acceptable resolution and improved sensitivity (0.005-0.02 μg/mL vs. 0.04 μg/mL). The proposed method was also applied to pharmacokinetic research: accelerated solvent extraction (ASE) was used to improve the extraction efficiency, which prepared extract much faster and more pure than conventional methods. As the pharmacokinetic parameters indicated, the monolithic capillary electro-chromatography method was efficient, sensitive, specific, and durable, guaranteeing its utility for the determination of multiple structure-related compounds in rat plasma.

Discovery and mechanistic study of Imperatorin that inhibits HBsAg expression and cccDNA transcription

“…One of the compounds that emerged from the screening was Imperatorin, a furanocoumarin compound found in the root of angelica dahurica, 10 radix saposhnikoviae, 11 fructus cnidii, 12 and other umbelliferae plants. Imperatorin has been noted for its diverse range of pharmacological effects, including anti-inflammatory, [13][14][15] anticancer, 16,17 anti-coagulant, 18 and antibacterial.…”

“…In this study, a Chinese herb library and 966 natural products related to liver disease were screened to identify novel and natural drug candidates capable of blocking HBsAg production from cccDNA. One of the compounds that emerged from the screening was Imperatorin, a furanocoumarin compound found in the root of angelica dahurica , 10 radix saposhnikoviae , 11 fructus cnidii , 12 and other umbelliferae plants. Imperatorin has been noted for its diverse range of pharmacological effects, including anti‐inflammatory, 13–15 anticancer, 16,17 anti‐coagulant, 18 and antibacterial 19,20 .…”