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  • Title: Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion studies of sweroside in rats.
    Author: Sheng N, Yuan L, Zhi X, Cui C, Zhang Z, Jia P, Zhang X, Zhang L, Wang X.
    Journal: J Chromatogr B Analyt Technol Biomed Life Sci; 2014 Oct 15; 969():1-11. PubMed ID: 25128643.
    Abstract:
    A sensitive, reliable and accurate high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the quantification of sweroside in rat plasma, tissue and excretion. A single-step protein precipitation by methanol was used to prepare samples. Sweroside and swertiamarin (internal standard, IS) were separated by using a C18 column and a mobile phase consisted of methanol and water containing 0.1% formic acid running at a flow rate of 0.8ml/min for 6min. Detection and quantification were performed using a mass spectrometer by the multiple-reaction monitoring (MRM) in positive electrospray ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were [M+H](+)359.1→197.2 for sweroside and [M+Na](+)397.4→165.3 for swertiamarin (IS), respectively. The inter-day precision (RSD %) was less than 11.20% and intra-day precision (RSD %) was less than 10.90%, while the inter-day accuracy (RE %) was ranged from -9.69 to 9.17% and intra-day accuracy (RE %) was ranged from -10.56 to 13.47%. The mean elimination half-life (t1/2) of sweroside for 5, 10 and 15mg/kg dose were 78.8, 67.6 and 77.2min, respectively. And sweroside follows linear plasma pharmacokinetics across the investigated dosage range in rats (5-15mg/kg). The absolute bioavailability (F %) of sweroside was 11.90% on average. The results of tissue distribution showed the higher sweroside concentrations were found in kidney, liver, spleen and lung, and the small amount of drug was distributed into the brain tissue. The high distribution in liver confirms the reports that sweroside has hepatoprotective activity and promoted liver regeneration, and there was no long-term accumulation of sweroside in rat tissues. Total recoveries of sweroside within 48h were 0.67% in bile, 1.55% in urine and 0.46% in feces, which might be resulted from liver first-pass effect. The above results suggested that sweroside was mainly excreted as the metabolites.
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