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

Abstract

Two valine carbamate prodrugs of daidzein were designed to improve its bioavailability. To compare the pharmacokinetic behavior of these prodrugs with different protected phenolic hydroxyl groups of daidzein, a rapid and sensitive method for simultaneous quantification of daidzein, its valine carbamate prodrug, and daidzein-7-O-glucuronide in rat plasma was developed and validated in this study. The samples were processed using a fast one-step protein precipitation method with methanol added to 50 μL of plasma and were analyzed by ultra-high performance liquid chromatography with tandem mass spectrometry. To improve the selectivity, peak shape, and peak elution, several key factors, especially stationary phase and the composition of the mobile phase, were tested, and the analysis was performed using the Kinetex R C18 column (100 × 2.1 mm, 2.6 μm) within only 2.6 min under optimal conditions. The established method exhibited good linearity over the concentration range of 2.0-1000 ng/mL for daidzein, and 8.0-4000 ng/mL for the prodrug and daidzein-7-O-glucuronide. The accuracy of the quality control samples was between 95.5 and 110.2% with satisfactory intra-and interday precision (relative standard deviation values < 10.85%), respectively. This sensitive, rapid, low-cost, and highthroughput method was successfully applied to compare the pharmacokinetic behavior of different daidzein carbamate prodrugs.

In‐depth analysis of the xanthine oxidase inhibitors of Cicer arietinum L.‐based receptor–ligand affinity coupled with complex chromatography

“…The experimentally obtained [M + H] + ( m/z ) values for compounds 1 – 3 were 417.3461, 255.0613 and 285.2619, respectively. By comparing the MS data and the LC retention times, the target compounds, daidzin, daidzein and calycosin, were identified 37–39 …”

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

“…Over the years, several methods of extraction and determination have been investigated for the analysis of DAN 16–20 but very few analytical methods have been developed for simultaneous quantification of DAN and its intact conjugated metabolites in biological matrices. An HPLC method developed by Hosoda et al 21 was conducted to evaluate soy isoflavones and their phase II metabolite concentrations in human plasma.…”

“…22 Moreover, 500 μL plasma was required for preparation of samples involving an extremely complicated method. Recently, our group developed the UPLC-MS/MS method for detection of DAN, its prodrug and DAN-7-G. 17 However, the method had higher LLOQ and could not be applied for analysis of DAN-7-4′-DS and 4′-I-P. Therefore, the requirement for a simple, reliable and sensitive analytical method for simultaneous evaluation of DAN, its prodrug, and DAN-7-4′-DS and DAN-7-G metabolites is essential.…”