Simultaneous Determination of Seven Components in Rat Plasma by the UPLC-MS/MS Method and Application of Pharmacokinetic Studies to SimiaoYong’an Decoction

Abstract

SimiaoYong’an Decoction (SYD) is a classical traditional Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. We developed a sensitive ultra-performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) method for the simultaneous determination of seven major active ingredients of SYD extract (i.e., harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C and harpagoside) in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard such as linarin, followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC® BEH C18 column (100 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min with methanol/water 0.1% formic acid aqueous (v/v) as the mobile phase. Detection was performed on a triple quadrupole tandem MS (QqQ-MS) via negative ion electrospray ionization in multiple reactions monitoring (MRM) mode. All calibration curves showed good linearity (r > 0.99) over the concentration range with a low limit of quantification between 0.029 and 5.813 ng/mL. Precision was evaluated by intra-day and inter-day assays, and the percentages of the RSD were all within 8.1%. The extraction efficiency and matrix effect were 80.6–113.6% and 82.9–99.5%, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of SYD extract and the corresponding single and combined traditional Chinese medicines (TCMs). The pharmacokinetic properties of the seven ingredients showed dynamic changes due to counteraction among the different coexisting components. The established approach has proven useful in the study of the active constituents in a traditional Chinese prescription.

Pharmacokinetics, Bioavailability, and Tissue Distribution Study of Angoroside C and Its Metabolite Ferulic Acid in Rat Using UPLC-MS/MS

“…To date, some HPLC methods were applied in determine angoroside C in Radix Scrophulariae ( Yang et al, 2009 ; Zhang et al, 2011 ), and only one paper reported the LC-MS/MS method to determine multi-components including angoroside C in plasma after intragastric SimiaoYong′an decoction to rat ( Liu et al, 2017a ). But beyond that, no significant ADME studies have been published in the literature on angoroside C and its metabolites in vivo .…”

Simultaneous high‐performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill

“…However, these components were not detectable in rat plasma after oral administration of 2500 mg/kg YGP. Considering their lower contents in YGP (for example, 0.97 μg/g for mesaconine and 2.1 μg/g for benzoylaconitine), lower absorption/bioavailability and extensive in vivo metabolism (for example, loganin , mesaconine , and fuziline ), these results are reasonable.…”

Si-Miao-Yong-An Decoction Protects Against Cardiac Hypertrophy and Dysfunction by Inhibiting Platelet Aggregation and Activation

“…As a result, 14 compounds were preliminary identified, of which 10 compounds were prototypes of SMYAD, and four were metabolites (Chi et al, 2016). In addition, seven major active ingredients of SMYAD extract (i.e., harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C, harpagoside) in rat plasma were detected simultaneously by a sensitive ultra-performance liquid chromatography–tandem mass spectrometry method (Liu et al, 2017a).…”