Determination of toosendanin in rat plasma by ultra-performance liquid chromatography-electrospray ionization-mass spectrometry and its application in a pharmacokinetic study.
Toosendanin (TSN) is a major triterpenoid existing in Melia toosendan, which has been used as a digestive tract parasiticide and insecticide but with serious hepatotoxicity. An ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method was developed for determination of TSN in rat plasma. Plasma samples were separated on Acquity UPLC(TM) BEH C(18) column with acetonitrile and water as flow phase by gradient elution and determined by quadrupole mass spectrometer in negative selective ion monitoring mode. Usolic acid was used as internal standard. The calibration curves were linear over 0.02-3.0 µg/mL for TSN with a lower limit of quantification (LLOQ) of 20 ng/mL in rat plasma. The extraction recoveries of TSN were within 74.3-80.7% with an accuracy of 94.5-108.9%. The intra- and inter-day precision values of the assay at three quality control levels were 8.8-13.8% and <13.9% at LLOQ level, respectively. The method was successfully applied to a pharmacokinetic study of TSN in rats after a single intravenous and oral administration of 2 and 60 mg/kg. The shorter T(max) , higher V(d) and Cl of TSN after oral administration indicated that TSN could be absorbed, distributed and eliminated quickly in rats in vivo. The absolute bioavailability of TSN after oral administration was 9.9%.
Department of Pharmacognosy, China Pharmaceutical University, Nanjing,China.
Xintang
X
Wang
Changhong
C
Wang
Zhengtao
Z
Wang
D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014315:Triterpenes
D004365:Drugs, Chinese Herbal; C036454:toosendanin; D014315:Triterpenes