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

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 × 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 × 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.