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.
Highlights
SimiaoYong’an Decoction (SYD) is a classical Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation
The UPLC-MS/MS method described here was developed to facilitate the simultaneous quantification of harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C, harpagoside and IS in rat plasma
The validated UPLC-MS/MS method was successfully applied to pharmacokinetic studies of harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C and harpagoside in plasma samples obtained from SD rats that had been orally administered 15 groups of extracts of SYD and its single and combined traditional Chinese medicines (TCMs) (LJ, Scrophularia ningpoensis Hemsl. (SN), Angelica sinensis (Oliv.) Diels (AS), Glycyrrhiza uralensisFisch. (GU), Lonicera japonica Thunb. (LJ) + SN, LJ + AS, LJ + GU, SN + AS, SN + GU, AS + GU, LJ + SN + AS, LJ + SN + GU, LJ + AS + GU, SN + AS + GU and SYD)
Summary
SimiaoYong’an Decoction (SYD) is a classical Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. Many types of compounds have been reported in herbs composing SYD [6,7,8,9,10,11], including flavonoids (i.e., liquiritin), iridoids (i.e., harpagide, sweroside, loganin and harpagoside), phenylpropanoids (i.e., angoroside C and chlorogenic acid), terpenoids and others. HPLC-MS and pharmacokinetic studies referred to harpagide [21], chlorogenic acid [18], sweroside [22], loganin [23], liquiritin [24], angoroside C [25] and harpagoside [25] have been reported. Seven characteristic compounds from three chemical types, such as flavonoids (i.e., liquiritin), iridoids (i.e., harpagide, sweroside, loganin and harpagoside) and phenylpropanoids (i.e., angoroside C and chlorogenic acid), were selected as reference analytes for integral pharmacokinetic studies of SYD.
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