Simultaneous determination of daidzein, its prodrug and major conjugative metabolites in rat plasma and application in a pharmacokinetic study

Abstract

An isoleucine carbamate prodrug of daidzein was designed to address the challenge of its metabolic instability with the aim of improving oral bioavailability. To explore the process of biotransformation between...

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability

“…The inhibition assay was performed to evaluate if 5 mM Glysar could inhibit 50 μM DAN and D-4′-I uptake mediated by PEPT1 . In addition, 50 mM ES and FEX were used to determine their inhibitory effect on DAN and D-4′-I (50 μM) uptake mediated by OATP. , All the samples were determined by high-performance liquid chromatography–dual mass spectrometry (HPLC–MS/MS) as previously described . Briefly, the method was performed on a Nexera XR HPLC instrument coupled with an LCMS-8060 triple-quadrupole tandem mass spectrometer (Shimadzu, Kyoto, Japan).…”

“…Subsequently, 100 μL of the supernatant was added to 1 μL of acetic acid. Mixtures were vortexed immediately for 30 s and stored at −80 °C until HPLC–MS/MS analysis …”

“…34,35 All the samples were determined by high-performance liquid chromatography−dual mass spectrometry (HPLC−MS/MS) as previously described. 36 Briefly, the method was performed on a Nexera XR HPLC instrument coupled with an LCMS-8060 triple-quadrupole tandem mass spectrometer (Shimadzu, Kyoto, Japan). Chromatographic separation was achieved on a Kinetex C18 column (100 × 2.1 mm, 2.6 μm) with a gradient elution method (Table S1).…”

“…Mixtures were vortexed immediately for 30 s and stored at −80 °C until HPLC−MS/MS analysis. 36 Antihepatitis Activities in Vivo. The pharmacodynamics study in mice was conducted in accordance with the protocol approved by the Animal Care and Use Committee of Shenyang Pharmaceutical University (SYPU-IACUC-C2021-9-3-106).…”