A UPLC–MS/MS approach for simultaneous determination of eight flavonoids in rat plasma, and its application to pharmacokinetic studies of Fu‐Zhu‐Jiang‐Tang tablet in rats

Abstract

The purpose of this study is to establish and validate a UPLC-MS/MS approach to determine eight flavonoids in biological samples and apply the method to pharmacokinetic study of Fu-Zhu-Jiang-Tang tablet. A Waters BEH C UPLC column was employed with methanol/0.1% formic acid-water as mobile phases. The mass analysis was carried out in a triple quadrupole mass spectrometer using multiple reaction monitoring with negative scan mode. A one-step protein precipitation by methanol was used to extract the analytes from blood. Eight major flavonoids were selected as markers. Our results showed that calibration curves for 3'-hydroxypuerarin, mirificin, puerarin, 3'-methoxypuerarin, daidzin, rutin, astragalin and daidzein displayed good linear regression (r > 0.9986). The intra-day and inter-day precisions (RSD) of the eight flavonoids at high, medium and low levels were <8.03% and the bias of the accuracies ranged from -5.20 to 6.75%.The extraction recoveries of the eight flavonoids were from 91.4 to 100.5% and the matrix effects ranged from 89.8 to 103.8%. The validated approach was successfully applied to a pharmacokinetic study in Sprague-Dawley rats after oral administration of FZJT tablet. Double peaks were emerged in curves of mean plasma concentration for 3'-methoxypuerarin, which was reported for the first time.

Pharmacokinetic Comparisons of Different Combinations of Yigan Jiangzhi Formula in Rats: Simultaneous Determination of Fourteen Components by UPLC-MS/MS

“…Meanwhile, a bimodal phenomenon of 3 flavonoids (daidzein, apigenin, and luteolin) was presented in Figure 4. In accordance with what had been reported previously [36][37][38], the first peak appeared in less than 1 h and the second peak at about 5 h or even later probably due to distribution, reabsorption, and enterohepatic circulation [39][40][41].…”

Astragalin: a food-origin flavonoid with therapeutic effect for multiple diseases

“…An increasing number of studies have been conducted on the pharmacokinetics of AG in vivo in recent years, and the pharmacokinetic parameters of the relevant studies are shown in Table 3 . Tao et al reported that the time to the maximum concentration (T max ) of AG in the Fu-Zhu-Jiang-Tang total fraction in rats was 0.39 ± 0.14h, and the elimination half time (T 1/2 ) of AG was 0.31 ± 0.04 h ( Tao et al, 2017 ); He et al reported that the T max of AG in total flavonoids from mulberry leaves was 0.19 ± 0.06h, and the T 1/2 of AG was 0.87 ± 0.52 h ( He et al, 2013 ); and Xu et al observed that AG was absorbed from the gastrointestinal tract of the rat and was in the plasma for 5 min after it was detected( Xu et al, 2018 ), indicating that AG was absorbed and eliminated faster in the rat. Compared with the normal group, the myocardial ischemia–reperfusion injury (MIRI) rats exhibited higher T max , C max , AUC (0-t) , AUC (0-∞) , MRT (0-t) , and MRT (0-∞) and lower CL ( Zheng et al, 2020 ).…”

“…An increasing number of studies have been conducted on the pharmacokinetics of AG in vivo in recent years, and the pharmacokinetic parameters of the relevant studies are shown in Table 3. Tao et al reported that the time to the maximum concentration (T max ) of AG in the Fu-Zhu-Jiang-Tang total fraction in rats was 0.39 ± 0.14h, and the elimination half time (T 1/2 ) of AG was 0.31 ± 0.04 h (Tao et al, 2017); He et al reported that the T max of AG in total flavonoids from mulberry leaves was 0.19 ± 0.06h, and the T 1/2 of AG was 0.87 ± 0.52 h (He et al, 2013);…”

Development of a liquid chromatography–tandem mass spectrometry method for simultaneous determination of five isoflavonoids and seven neurochemicals in rat brain dialysate and its application to a pharmacological study

“…Highly sensitive and selective bioanalytical methods are required for microdialysate assay and the most commonly used technique is LC–MS/MS . Several analytical approaches have been established for determination of isoflavonoids from pueraria radix or special neurochemicals in biological matrixes . However, there are no available methods for simultaneous determination of the interested multiple isoflavonoids and neurotransmitters in vivo.…”