Abstract
Panax notoginseng saponin (PNS) is the main active gradient of Chinese traditional medicine Panax notoginseng. Although its prominent therapeutic efficacy has been demonstrated by various researchers, the broader application is restricted by the low bioavailability of PNS. This article aims to discuss PNS's plasma pharmacokinetics after oral administration of bio-adhesive tablet of PNS to beagle dogs and improve its bioavailability in comparison with normal tablet. The bio-adhesive tablet was prepared according to our previous patent, using chitosan as main excipient. A simple and sensitive LC-MS/MS combined with solid-phase extraction (SPE) method for the analysis of PNS in dog's plasma was developed in our previous study, and was validated to apply in the pharmacokinetics study in this work. Three ingredients: Notoginsenoside R1 (R1), Ginsenoside Rg1 (Rg1) and Ginsenoside Rb1 (Rb1) (Figure 1), were chosen as indicators of PNS to analyze it in vivo. Statistically significant increase (P < 0.05) in pharmacokinetic parameters of PNS including AUC and Tmax for R1, Rg1 and Rb1, Cmax for R1 and Rb1, MRT for Rg1 were obtained after oral administration of bio-adhesive tablet of PNS comparing with its normal tablet. The formulation modification of using chitosan to prepare bio-adhesive tablet for oral administration is effective in improving the bioavailability of PNS, thereby enhancing its potential therapeutic effect and broadening its clinical application.
Highlights
Validation of LC-MS/MS methods The specificity was evaluated by comparing chromatograms of blank plasma, blank plasma spiked with R1, Rg1, Rb1, internal standard, and plasma samples after oral administration of by bio-adhesive tablet of Panax notoginseng saponin (PNS)
The accuracy and precision were evaluated by quality control samples at low (2.8 ng/ml for R1, 3.8 ng/ml for Rg1 and ng/ml for Rb1), medium (14 ng/ml for R1, ng/ml for Rg1 and 180 ng/ml for Rb1), and high (140 ng/ml for R1, 190 ng/ml for Rg1 and 900 ng/ml for Rb1) concentrations which were prepared in the same way as calibration standards
The intra-batch accuracy and precision of the assay were assessed by quality control samples analysis at three concentrations in six replicates and the inter-batch was detected by analyzing them in three batches
Summary
Based on the consideration of choosing an excipient with lower toxicity, in this study we used chitosan to prepare bio-adhesive tablet. Reported detection method simultaneously analyzed Notoginsenoside R1, Ginsenoside Rg1, Rd, Re and Rb1 in rat plasma by HPLC/ESI/MS [14], their sample preparation method using liquid-liquid extraction is different from our solid-phase extraction (SPE) method. We adopted a liquid chromatography-tandem mass spectrometry (LC/MS/MS) combined with SPE method established in our previous study to simultaneously detect Notoginsenoside R1, Ginsenoside Rg1 and Rb1 to reflect the veritable pharmacokingetics properties of PNS in plasma sample of beagle dogs [15]. It is expected that this research would be effective for improving bioavailability of PNS and their clinical therapeutic efficacy, and can serve as a significant foundation for further pharmacological studies of PNS
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