Determination and pharmacokinetics of DT-13 in rat plasma by LC-MS

A sensitive and specific LC-MS assay for DT-13 in rat plasma was developed. DT-13 is an active steroidal saponin present in Liriopes Radix and is developed as an anti-tumor drug candidate. The samples were extracted by acetonitrile-mediated plasma protein precipitation. The chromatographic separation was carried out using a Ultimate C-18 column (250 mm x 4.6 mm, id., 5 mu m) with a mobile phase composed of acetonitrile: 5 mmol/L aqueous ammonium acetate (60:40, v:v). The method was validated and the specificity, linearity (r(2) = 0.9980 within 10-1000 ng/mL), lower limit of quantitation (LLOQ 10 ng/mL), precision (intra- and inter-day <12.3%), accuracy (93.4-106.3%), recovery (91.0 +/- 4.7%) and stability were determined. The method was applied to the pharmacokinetic study of DT-13 in rat plasma after intravenous and intragastric administration. The results showed DT-13 underwent a prolonged absorption and slow elimination with a low oral bioavailability (5.51%) in rats. (C) 2011 Elsevier B.V. All rights reserved.