UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder

Abstract

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP.

Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

“…The recipe for Xiaoyao Powder was first recorded in "Taiping Huimin Heji Jufang", one of the earlier pharmacopoeia from Song Dynasty in China [23]. In this TCM study, our modified recipe consists of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Rhizoma Zingiberis Recens, Radix Glycyrrhizae Preparata and Herba Menthae in a ratio of 5:5:5:5:5:5:4:1.…”

“…This Xiaoyao Powder solution was subjected to ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), and 16 common fingerprint peaks were defined and identified. Fourteen target compounds, such as saikosaponin c, albiflorin, paeoniflorin, quercetin, and ferulic acid, were characterized distinctly in the plasma from rats orally administrated the Xiaoyao Powder solution rat as determined by UPLC-MS/MS [23,25]. In this study, chronic hepatic toxicity investigation of a modified recipe solution was carried out by injecting the solution to mice.…”

Tissue distribution and molecular docking research on the active components of Bidens bipinnata L. against hyperlipidemia

“…In addition, the kidney distribution features between flavonoid glycosides and flavonoid aglycones were different, and the maximum concentration of quercetin was significantly higher than that of other flavonoids. By summarizing the literature (Xu et al, 2018; Zhang et al, 2019), it can be seen that, as flavonoid glycosides, rutin and hyperoside could be hydrolyzed to the corresponding aglycone quercetin in vivo , leading to less absorption in the prototype form. They were also readily metabolized via the liver to form glucuronide and other metabolites after entering the circulation and subsequently eliminated in metabolites via the kidney.…”

“…From Figure 3, we also found that the concentration of flavonoids in many tested tissues increased again after decreasing to a certain extent, which was in accordance with the double peak phenomenon in the plasma concentration–time curves of flavonoid reported previously. The phenomenon may be caused by enterohepatic recirculation, hydrolysis, extensive metabolism and mutual conversion of flavonoids in vivo (Xu et al, 2018).…”

Pharmacokinetics of Eight Flavonoids in Rats Assayed by UPLC-MS/MS after Oral Administration of Drynariae rhizoma Extract

“…The method was validated in terms of specificity, linearity, lower limit of detection (LLOD), lower limit of quantification (LLOQ), accuracy and precision, extraction recovery, stability, and matrix effects based on the method validation procedure in the previous work [15].…”