An LC‐MS/MS method for determination of 3,6′‐disinapoylsucrose in rat plasma and its application to a pharmacokinetic study

Abstract

3,6'-Disinapoylsucrose (DSS), a major active component of traditional Chinese medicine Yuan-Zhi (the roots of Polygala tenuifolia), has significant effects for neuroprotection and improving learning memory. In order to explore the pharmacokinetic properties of DSS so as to further understand its in vivo activities, a sensitive LC-MS/MS method was developed for determination of DSS in rat plasma and applied to a pharmacokinetic study in the present study. After treatment by protein precipitation, the plasma sample was separated on a C(18) HPLC column and analyzed by a mass spectrometry under positive electrospray ionization. Multiple-reaction monitoring was employed to measure the ion transition at m/z 777.4 --> 409.2 for DSS and m/z 557.2 --> 309.1 for forsythin as internal standard. The method was linear over the studied concentration range of 0.5-1000.0 ng/mL. The precision and accuracy ranged from 1.4 to 18.4%, and from -3.7 to -9.5%, respectively, for within-day and between-day assay. Extraction recovery was higher than 86.6%. The limits of detection and quantification were 0.3 and 0.5 ng/mL, respectively. The present method was successfully applied to a pharmacokinetic study. DSS was found to have poor oral absorption with only about 0.5% bioavailability.

Intestinal Transport of 3,6′-Disinapoylsucrose, A Major Active Component of Polygala tenuifolia, Using Caco-2 Cell Monolayer and In Situ Rat Intestinal Perfusion Models

“…Its average Papp value for transporting across the small intestine greatly changed from (3.97 ± 0.41) × 10 −6 to (23.4 ± 4.5) × 10 −6 and (20.0 ± 1.8) × 10 −6 cm/s, respectively, in the presence of EDTA (17 mM) and sodium caprate (5.14 mM). This result is consistent with that observed in the Caco-2 cell monolayer model and further confirmed that the paracellular penetration might be the main pathway for DSS transport across the small intestine [26], which might be the main reason for DSSʼs poor oral bioavailability with only 0.5 % of the dose [13]. To explore the reasons for its poor bioavailability, the stability of DSS in the gastrointestinal tract was investigated by incubation of the gastrointestinal contents at 37°C.…”

“…Our previous studies have demonstrated that DSS is poorly absorbed orally, with absolute bioavailability only around 0.5 % of the dose in rats [13]. In order to explore the reasons for its poor bioavailability and to further understand its pharmacokinetic properties, the present study was performed to investigate the intestinal transport mechanism of DSS by using in vitro Caco-2 cell monolayer and in situ rat intestinal perfusion models.…”

“…The degradation products, e.g., the metabolites of DSS in the gastrointestinal tract were not identified in the present study. Based on our previous results on DSS pharmacokinetic properties [13], it is speculated that DSS might be absorbed mainly in the small intestine rather than in the colon, since the T max (time to peak plasma concentration) of DSS was estimated at 30 min after oral administration. Therefore, the degradation of DSS in the colon might not be the main reason for its poor oral bioavailability, but rather the main reason might be its paracellular transport across the intestine mucosa.…”

Simultaneous analysis of polygala acid, senegenin and 3,6′‐disinapoylsucrose in rat plasma by liquid chromatography–tandem mass spectrometry: application to a pharmacokinetic study after oral administration

“…In this study, we have developed and validated a rapid, specific and sensitive LC‐MS/MS method for simultaneous determination of polygala acid, senegenin and DSS in rat plasma using forsythin (Fig. D) as internal standard (IS; Chen et al ., ). This method was applied to a pharmacokinetic study after oral administration of polygala acid, senegenin and DSS.…”

A rapid and sensitive HPLC–MS/MS analysis and preliminary pharmacokinetic characterization of sibiricaxanthone F in rats

“…This atypical drug absorption profiles such as multiple peaks and window-type absorption profiles were also encountered in berberine, macranthoidin B, 3,6 -disinapoylsucrose, tacrolimus, etc. [25][26][27][28][29]. Further detailed absorption investigations are needed to elucidate the mechanism of the multiple peak phenomenon in the next step.…”