Quantitative determination of the anticancer agent tubeimoside I in rat plasma by liquid chromatography coupled with mass spectrometry
Quantitative determination of the anticancer agent tubeimoside I in rat plasma by liquid chromatography coupled with mass spectrometry
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DOI：
10.1016/j.jchromb.2006.07.053
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发表时间：
2007-01-01
影响因子：
3
通讯作者：
Chen, Chun-Lin
中科院分区：
文献类型：
--
作者：
Liang, Ming-Jin;Zhang, Wei-Dong;Chen, Chun-Lin
土贝母苷I是土贝母中分离得到的重要成分。土贝母皂苷I具有抗炎、抗肿瘤、抗肿瘤等多种药理活性。采用液相色谱-质谱联用定量检测法（LC/MS）研究土贝母皂苷I在大鼠体内的药代动力学和生物利用度。分析前，将血浆样品脱蛋白、蒸发并在100 μ l甲醇中复溶。通过沃茨对称（（R））C18反相柱（3.5 μ m，150 mm × 2.1 mm，沃茨公司，USA）和SB-C18保护柱（5 μ m，20 mm × 4.0 mm）。移动的相是含有5 μ M NaAc（60：40，v/v）的乙腈和水的混合物。方法在20-5000 ng/ml浓度范围内进行验证，校准曲线线性相关系数> 0.999。土贝母皂苷I的最低定量限（LLOQ）为20 ng/ml（0.1 ml大鼠血浆）。批内准确度和精密度范围分别为92.4 - 104.9%和5.8 - 10.5%，而批间准确度和精密度范围分别为94.2 - 95.0%和5.1 - 8.8%。该方法进一步应用于大鼠静脉和口服土贝母苷I后的药代动力学和口服生物利用度。土贝母皂苷I的口服生物利用度仅为0.23%，表明土贝母皂苷1吸收较差或发生酸诱导降解。在大鼠静脉和经口给药后的初步药代动力学研究中证实了这种新的LC/MS方法的实用性。(c)2006 Elsevier B. V.保留所有权利。
Tubeimoside I is an important component isolated from Bolbostemma paniculatum. Tubeimoside I has been demonstrated to possess many pharmacological activities, including anti-inflammatory, antitumor, and antitumor-promoting effects. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of tubeimoside I in rats by using a liquid chromatography coupled with mass spectrometry quantitative detection method (LC/MS). The plasma samples were deproteinated, evaporated and reconstituted in 100 mu l methanol prior to analysis. The separation was performed by Waters Symmetry((R)) C18 reversed-phase column (3.5 mu m, 150 mm x 2.1 mm, Waters Inc., USA) and a SB-C18 guard column (5 mu m, 20 mm x 4.0 mm). The mobile phase was a mixture of acetonitrile and water containing 5 mu M NaAc (60:40, v/v). The method was validated within the concentration range 20-5000 ng/ml, and the calibration curves were linear with correlation coefficients > 0.999. The lowest limit of quantitation (LLOQ) for tubeimoside I was 20 ng/ml in 0.1 ml rat plasma. The intra-assay accuracy and precision ranged from 92.4 to 104.9% and from 5.8 to 10.5%, respectively, while inter-assay accuracy and precision ranged from 94.2 to 95.0% and from 5.1 to 8.8%, respectively. The method was further applied to assess pharmacokinetics and oral bioavailability of tubeimoside I after intravenous and oral administration to rats. The oral bioavailability of tubeimoside I is only 0.23%, which indicates that tubeimoside 1 has poor absorption or undergoes acid-induced degradation. Practical utility of this new LC/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration. (c) 2006 Elsevier B.V. All rights reserved.