A sensitive, high‐throughput, and eco‐friendly analysis of daidzein and its valine carbamate prodrug in rat plasma by supercritical fluid chromatography with tandem mass spectrometry

Abstract

A valine carbamate prodrug of daidzein was synthesized to improve its bioavailability because of the poor solubility and low permeability of daidzein. To evaluate the pharmacokinetic behavior of the prodrug, a sensitive and high-throughput method was developed and validated for the simultaneous determination of daidzein and its prodrug in rat plasma. The samples were extracted by ethyl acetate and then analyzed by a supercritical fluid chromatography with electrospray ionization tandem mass spectrometry method. The separation was achieved by an ACQUITY UPC ™ BEH 2-EP column maintained at 40°C using carbon dioxide (≥99.99%) and methanol within 3.0 min by gradient elution. The mass transition ion pairs were m/z 254.8→136.7, 398.0→254.9, and 271.0→91.07 for daidzein, the prodrug, and genistein, respectively. The calibration curves were linear over the concentration ranges of 2-500 (r > 0.997) and 10.0-5000.0 ng/mL (r > 0.996) with lower limits of quantification of 2 and 10 ng/mL for daidzein and the prodrug, respectively. The intra- and interday accuracy and precision were within ±15% for all quality control samples. This developed method enabled high specificity, low cost, low solvent consumption, and a brief analysis time and was successfully applied to a bioavailability evaluation of daidzein and its carbamate prodrug.

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

“…However, extremely severe phase II metabolism of DAN results in its low bioavailability, which limits clinical and other applications. 9,10 Prodrug technology is an effective strategy to protect drugs from phase II metabolism, 11 and amino acids as modified groups can enhance the water solubility of parent drugs. 12 In this study, a 4 0 -O-L-isoleucyl carbamate prodrug of DAN (4 0 -I-P, Fig.…”

“…Prodrug technology is an effective strategy to protect drugs from phase II metabolism, 11 and amino acids as modified groups can enhance the water solubility of parent drugs. 12 In this study, a 4′-O-L-isoleucyl carbamate prodrug of DAN (4′-I-P, Fig.…”

A rapid ultra high performance liquid chromatography–tandem mass spectrometry method for the quantification of daidzein, its valine carbamate prodrug, and glucuronide in rat plasma samples: Comparison of the pharmacokinetic behavior of daidzine valine carbamate prodrugs

“…To overcome these limitations, two carbamate prodrugs were synthesized in our lab through introducing l-valyl group to 4ť-or 7-phenolic hydroxyl groups of DAN, thereby generating 4′-O-l-valyl carbamate prodrug (4′-L-P) and 7-O-l-valyl carbamate prodrug (7-L-P) of DAN (Figure 1) [12,13]. Although these modifications improved the oral absorption of DAN to different extents, but the stability and pharmacokinetic behavior of these prodrugs with different protected positions for the phenolic hydroxyl groups of DAN, and their effect on the glucuronidation of DAN in vivo still remain unclear, despite being importance.…”

Development and optimization of a supercritical fluid chromatography tandem mass spectrometry method for the high‐throughput determination of nimodipine in beagle plasma

“…In addition, the density and solvent capability of supercritical fluids are similar to lipids, and their diffusion coefficient and viscosity are analogous to gas, which enables higher flow rate, faster column equilibration, and quick analysis . Recently, supercritical fluid chromatography MS/MS (SFC‐MS/MS) has been implemented in the separation and analysis of biological samples with satisfactory results . Based on these superior characteristics, SFC‐MS/MS is well suited for the determination of NMD in biological matrices.…”