title: Determination of astragaloside III in rat plasma by liquid chromatography-tandem mass spectrometry and its application to a rat pharmacokinetic study.
abstract: Astragaloside III (AST III), a naturally occurring saponin compound isolated from Radix Astragali, has been demonstrated to have anti-gastric ulcer, immunomodulatory and antitumor effects. To evaluate its pharmacokinetics in rats, a rapid, sensitive and specific high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method has been developed and validated for the quantification of astragaloside III in rat plasma. Samples were pretreated using a simple protein precipitation with methanol-acetonitrile (50:50, v/v) and the chromatographic separation was performed on a C18 column by a gradient elution using a mobile phase consisting of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. Astragaloside III and the internal standard (buspirone) were detected using a tandem mass spectrometer in positive multiple reaction monitoring mode. Method validation revealed excellent linearity over the range of 5.00-5000 ng/mL together with satisfactory intra- and inter-day precision, accuracy and recovery. Stability testing showed that astragaloside III spiked into rat plasma was stable for 24 h at 20°C temperature, for up to 30 days at -80°C, and during three freeze-thaw cycles. The method was successfully used to investigate the pharmacokinetic profile of AST III after oral (10 mg/kg) and intravenous (1.0 mg/kg) administration in rats. The oral absolute bioavailability of AST III was calculated to be 4.15 ± 0.67% with an elimination half-life value of 2.13 ± 0.11 h, suggesting its poor absorption and/or strong metabolism in vivo.
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Yongsong
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
authors.forename: Pengyue
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Manyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Muxin
authors.initials: M
authors.lastname: Gong
authors.affiliation: Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012503:Saponins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D012503:Saponins; C586938:astragaloside III
keywords: LC-ESI-MS/MS; astragaloside III; bioavailability; rat