Quantitative determination of Lx2-32c, a novel taxane derivative, in rat plasma by liquid chromatography-tandem mass spectrometry

A sensitive and reliable LC-MS/MS method for the determination of Lx2-32c, a novel taxane derived from cephalomannine, has been developed and validated. Plasma samples containing Lx2-32c and paclitaxel (internal standard) were prepared based on a simple protein precipitation by the addition of two volumes of acetonitrile. The analyte and internal standard were separated on a Zorbax SB-C18 column (3.5 mu m, 2.1 mm x 100 mm) with the mobile phase of acetonitrile/water containing 0.1% formic acid (v/v) with gradient elution at a flow rate of 0.2 ml/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with atmospheric pressure chemical ionization (APCI) by multiple reactions monitoring (MRM) of the transitions at m/z 887.5 -> 264.3 for Lx2-32c and 854.5 -> 286.2 for IS. Linear detection responses were obtained for Lx2-32c ranging from 1 to 1000 ng/ml. Inter- and intra-day precision (R.S.D.%) were all within 15% and the accuracy (R.E.%) was equal or lower than 8%. The lower limit of quantitation (LLOQ) was 1 ng/ml and the average recovery was greater than 91.5%. The method was successfully applied to the pharmacokinetic study of Lx2-32c in rat plasma. (C) 2013 Elsevier B.V. All rights reserved.