Simultaneous determination of eight analytes of Fuzheng Huayu recipe in beagle dog plasma by UHPLC–Q/exactive Orbitrap HRMS and its application to toxicokinetics

Abstract

Fuzheng Huayu recipe (FZHY) is a Chinese patent medicine for the treatment of liver fibrosis. This study aimed to investigate the toxicokinetics of FZHY in beagle dogs after oral administration. Blood samples were collected on days 1, 15 and 28 after oral gavage of FZHY dosages of 400 or 1,200 mg/kg body weight once a day. A UHPLC-Q-Orbitrap method was developed and validated to simultaneously determine and quantify eight components of FZHY in beagle dog plasma. The times to peak concentration for eight components were18-120 min. The peak concentrations (C max ) of amygdalin, genistein, daidzein and 3,4-dihydroxybenzaldehyde were 1.43-43.50 ng/ml, the areas under the concentration-time curve (AUC (0-t) ) were 2.45-6,098.25 ng min/ml, and the apparent volumes of distribution (V d ) were 0.05-131.23 Â 10 4 ml/kg. The values of C max of prunasin, schisantherin A, schisandrin A and schisandrin were 7.35-1,450.73 ng/ml, the values of AUC (0-t) were 3,642.30-330,388.65 ng min/ml, and the values of V d were 11.15-1,087.18 Â 10 4 ml/kg. No obvious accumulation of the eight compounds was observed in beagle dogs. The results showed that the method is rapid, accurate and sensitive, and is suitable for detecting the eight analytes of FZHY. This study provides an important basis for the assessment of FZHY safety.

Pharmacokinetic study of five components of Fuzheng Huayu tablets in healthy human plasma

“…The pharmacokinetics of FZHY have been studied in rats and beagles. The plasma pharmacokinetics of eight components of FZHY, namely, schisandrin, schisandrin A, schisantherin A, amygdalin, genistein, 3,4‐dihydroxybenzaldehyde, daidzein, and prunasin, have been studied in beagles (Wang et al, 2022). In addition, the pharmacokinetics of six lignans in FZHY, including schisantherin A, schisandrin, schisandrin A, schisandrin C, schisandrol A, and schisandrol B, have been studied in a rat model, and four other components, namely, danshensu, salvianolic acid B, rosmarinic acid, and amygdalin, have also been studied in a rat model (Yang, Liu, Wang, et al, 2015; Yang, Liu, Zheng, et al, 2015).…”

“…After preliminary experiments, five FZHY components including amygdalin, prunasin, schisandrin, schisandrin A, and schisandrin B were selected for the pharmacokinetic study. We compared the pharmacokinetics of amygdalin, prunasin, schisandrin, and schisandrin A in humans, rats (Yang, Liu, Wang, et al, 2015; Yang, Liu, Zheng, et al, 2015), and dogs (Wang et al, 2022). The dosage for mice was close to half of that of humans in this experiment, whereas that for beagle dogs was almost double.…”

“…The method for the determination of the five components in human plasma was evaluated in terms of selectivity, linearity, detection limit, quantitative limit, matrix effects, precision, accuracy, and stability according to the guidance on bioanalytical method validation issued by the FDA (Wang et al, 2022).…”