Quantitative determination of the anticancer agent tubeimoside I in rat plasma by liquid chromatography coupled with mass spectrometry.
Tubeimoside I is an important component isolated from Bolbostemma paniculatum. Tubeimoside I has been demonstrated to possess many pharmacological activities, including anti-inflammatory, antitumor, and antitumor-promoting effects. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of tubeimoside I in rats by using a liquid chromatography coupled with mass spectrometry quantitative detection method (LC/MS). The plasma samples were deproteinated, evaporated and reconstituted in 100 microl methanol prior to analysis. The separation was performed by Waters Symmetry C18 reversed-phase column (3.5 microm, 150 mm x 2.1mm, Waters Inc., USA) and a SB-C18 guard column (5 microm, 20 mm x 4.0mm). The mobile phase was a mixture of acetonitrile and water containing 5 microM NaAc (60:40, v/v). The method was validated within the concentration range 20-5000 ng/ml, and the calibration curves were linear with correlation coefficients >0.999. The lowest limit of quantitation (LLOQ) for tubeimoside I was 20 ng/ml in 0.1 ml rat plasma. The intra-assay accuracy and precision ranged from 92.4 to 104.9% and from 5.8 to 10.5%, respectively, while inter-assay accuracy and precision ranged from 94.2 to 95.0% and from 5.1 to 8.8%, respectively. The method was further applied to assess pharmacokinetics and oral bioavailability of tubeimoside I after intravenous and oral administration to rats. The oral bioavailability of tubeimoside I is only 0.23%, which indicates that tubeimoside I has poor absorption or undergoes acid-induced degradation. Practical utility of this new LC/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration.
Liang
Ming-Jin
MJ
Department of Natural Medicinal Chemistry, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
Zhang
Wei-Dong
WD
Zhang
Chuan
C
Liu
Run-Hui
RH
Shen
Yun-Heng
YH
Li
Hui-Liang
HL
Wang
Xiao-Lin
XL
Wang
Xiang-Wei
XW
Zhu
Jian-Bao
JB
Chen
Chun-Lin
CL
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014315:Triterpenes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D012503:Saponins; D014315:Triterpenes; C051084:tubeimoside I