title: Quantitative determination of Lx2-32c, a novel taxane derivative, in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: 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 (3.5μm, 2.1mm×100mm) with the mobile phase of acetonitrile/water containing 0.1% formic acid (v/v) with gradient elution at a flow rate of 0.2ml/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 1000ng/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 1ng/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.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.forename: Feng
authors.initials: F
authors.lastname: You
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D019540:Area Under Curve; D002138:Calibration; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D019008:Drug Resistance, Neoplasm; D004355:Drug Stability; D057230:Limit of Detection; D008297:Male; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000097:blood; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D043823:Taxoids / Q000097:blood* / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D000970:Antineoplastic Agents; C532167:Lx2-32c compound; D043823:Taxoids; D014867:Water; D017239:Paclitaxel; C032159:acetonitrile
keywords: Bioavailability; LC–MS/MS; Lx2-32c; Pharmacokinetic; Taxane derivative