An LC‐MS/MS method for determination of curculigoside with anti‐osteoporotic activity in rat plasma and application to a pharmacokinetic study

Abstract

A rapid, simple, selective and sensitive LC-MS/MS method was developed for the determination of curculigoside in rat plasma. The analytical procedure involves extraction of curculigoside and syringin (internal standard, IS) from rat plasma with a one-step extraction method by protein precipitation. The chromatographic resolution was performed on an Agilent XDB-C18 column (4.6 × 50 mm, 5 µm) using an isocratic mobile phase of methanol with 0.1% formic acid and H2 O with 0.1% formic acid (45:55, v/v) at a flow rate of 0.35 mL/min with a total run time of 2.0 min. The assay was achieved under the multiple-reaction monitoring mode using positive electrospray ionization. Method validation was performed according to US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over 4.00-4000 ng/mL (R = 0.9984) for curculigoside with a lower limit of quantification of 4.00 ng/mL in rat plasma. The intra- and inter-day precisions and accuracies were 3.5-4.6 and 0.7-9.1%, in rat plasma, respectively. The validated LC-MS/MS method was successfully applied to a pharmacokinetic study of curculigoside in rats after a single intravenous and oral administration of 3.2 and 32 mg/kg. The absolute bioavailability of curculigoside after oral administration was 1.27%.

Pharmacokinetic and tissue distribution profile of curculigoside after oral and intravenously injection administration in rats by liquid chromatography–mass spectrometry

“…These results suggested that its bioavailability was independent of the doses. A recent study [9] reported that the absolute bioavailability of curculigoside was 1.27% in rats after oral administration at dose of 32 mg/kg. Therefore, it was also concluded that curculigoside might have a low absolute bioavailability.…”

“…Recently, an HPLC-MS/MS method has been developed to determine curculigoside in plasma and applied to pharmacokinetic study on rats [9]. However, the absorption characteristics, oral bioavailability and tissue distribution of curculigoside in vivo have not been investigated in detail.…”

The effects of verapamil on the pharmacokinetics of curculigoside in rats

“…Curculigoside (2 mg/mL) was dissolved in normal saline containing 0.5% methylcellulose and orally administered to rats at a dose of 20 mg/kg (Zhao et al 2014). The pretreated groups received oral verapamil (10 mg/kg) 30 min prior to curculigoside (Zhang et al 2015a(Zhang et al , 2015b.…”

“…There are several reasons for the poor bioavailability of a compound in the body, such as the low solubility and dissolution rate, poor permeability in intestine and fast elimination rate Shen et al 2015;Zhang et al 2015aZhang et al , 2015b. Several studies have been conducted to investigate the pharmacokinetic profiles of curculigoside in rats, and the results indicated that the oral bioavailability of curculigoside was poor (1-2%) (Zhao et al 2014;Yuan et al 2015). However, to the best of our knowledge, little information is available for the absorption and metabolic stability profiles of curculigoside, and the reason for its poor bioavailability.…”

“…Some research articles have also indicated that curculigoside could exert the effects of anti-osteoporosis, affecting bone formation and promoting fracture healing (Jiao et al 2009;Shen et al 2013;Liu et al 2014). However, the oral bioavailability of curculigoside was poor (Zhao et al 2014;Yuan et al 2015), which hinder its performance of pharmacological effects and clinical application.…”