LC–MS/MS Analysis and Pharmacokinetics of Daidzein and its 7-O-Glucuronide in Rats After Oral Administration of 7-O-L-Valyl Carbamate Prodrug

Abstract

Background: A valine carbamate prodrug (7-P) was designed to enhance the low bioavailability of daidzein due to its low water solubility and membrane permeability. Here, we developed a high-throughput HPLC–MS/MS method to measure daidzein and its 7-O-glucuronide after oral administration of daidzein or 7-P. Materials & methods: A HPLC–MS/MS method was validated and successfully applied to assess the pharmacokinetic behavior of daidzein and its 7-O-glucuronide after orally administrating daidzein or 7-P. The validated method on selectivity, linearity (r ≥ 0.995), precision (relative standard deviation <11.4%), accuracy (relative error <7.1%), extraction recovery (>92.4%), matrix effect (<8.2%) and stability were satisfied. Conclusion: The proposed economical, rapid and sensitive method will be an alternative analytical procedure for daidzein and its metabolite in biological samples.

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.…”

“…An HPLC-MS/MS method was reported by Soukup et al for the quantification of DAN and its metabolites, but this method requires a large volume of plasma (500 μL), a complicated pretreatment, and an elution time of 9.6 min for DAN-7-G [26]. Recently, Xu et al described an LC-MS/MS method for DAN and DAN-7-G with lower limit of quantification (LLOQ) of 2 and 10 ng/mL, respectively, and with a longer analytical time of 6 min [13]. However, none of the studies reported simultaneous quantification of DAN, its valine carbamate prodrug, and DAN-7-G.…”

“…Recently, Xu et al. described an LC‐MS/MS method for DAN and DAN‐7‐G with lower limit of quantification (LLOQ) of 2 and 10 ng/mL, respectively, and with a longer analytical time of 6 min [13]. However, none of the studies reported simultaneous quantification of DAN, its valine carbamate prodrug, and DAN‐7‐G.…”