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.
J Pharm Biomed Anal. 2014 Jan;88:483-8. doi: 10.1016/j.jpba.2013.09.018. Epub 2013 Oct 5.
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.
一种灵敏且可靠的 LC-MS/MS 法用于测定 Lx2-32c，这是一种来源于 Cephalomannine 的新型紫杉烷。已经建立并验证了该方法。含有 Lx2-32c 和紫杉醇（内标）的血浆样品通过加入两倍体积的乙腈进行简单的蛋白沉淀来制备。分析物和内标在 Zorbax SB-C18 柱（3.5μm，2.1mm×100mm）上分离，流动相为乙腈/水，含有 0.1%甲酸（v/v），以 0.2ml/min 的流速进行梯度洗脱。检测在配备大气压化学电离（APCI）的三重四极杆串联质谱仪上进行，通过 m/z 887.5→264.3 的跃迁进行多重反应监测（MRM）进行检测 Lx2-32c，IS 为 854.5→286.2。Lx2-32c 的线性检测响应范围为 1 至 1000ng/ml。日内和日间精密度（R.S.D.%）均在 15%以内，准确度（R.E.%）等于或低于 8%。定量下限（LLOQ）为 1ng/ml，平均回收率大于 91.5%。该方法成功应用于大鼠血浆中 Lx2-32c 的药代动力学研究。
