中文摘要：

目的建立测定紫杉醇含量的液相色谱-串联质谱联用方法,以此考察多聚（L-谷氨酸）-丙氨酸-紫杉醇偶合物在各种缓冲液和血浆中的稳定性。方法色谱条件：色谱柱：BetaBasicC18column（150mm×2.1mm,5μm）,流动相：乙腈-水-甲酸（65：35：0.1）,流速：0.2ml/min;质谱条件：电喷雾离子源,选择离子反应监测,正离子检测模式,前体药物-产物离子转换选择离子反应监测得出紫杉醇的质荷比m/z为854.2→286.1,内标多西紫杉醇的质荷比m/z为808.3→527.2。结果该检测方法的最低定量下限为0.5ng/ml,线性范围0.5～5000ng/ml,r=0.9980;多聚（L-谷氨酸）-丙氨酸-紫杉醇偶合物在醋酸盐缓冲液中的稳定性高于在磷酸盐中的稳定性,多聚（L-谷氨酸）-丙氨酸-紫杉醇偶合物在血浆中释放出紫杉醇的量明显高于其在醋酸盐和磷酸盐缓冲液中释放出紫杉醇的量。结论该方法特异性强、灵敏度高,成功应用于紫杉醇含量测定及多聚（L-谷氨酸）-丙氨酸-紫杉醇偶合物稳定性评价。

英文摘要：

Objective To establish a liquid chromatography-tandem mass spectrometric method for quantitative determination of paclitaxel,and to evaluate the stability of poly （L-glutamic acid）-alanine-paclitaxel conjugate in vitro.Methods Paclitaxel and internal standard docetaxel were separated on a BetaBasic C18 column （150 mm × 2.1 mm,5 μm） and quantified using a triple-quadrupole mass spectrometer operating in a positive ion electrospray selected reaction monitoring mode.The mobile phase was composed of acetonitrile：water：formic acid （65：35：0.1） with a flow rate of 0.2 ml/min.The assay was based on the selected reaction monitoring mode transitions at m/z of the precursor-product ion transitions m/z 854.2→286.1 for paclitaxel and 808.3→527.2 for docetaxel.Results The lower limit of quantification was 0.5 ng/ml,the linearity of the assay was assessed by calibration curves ranging from 0.5-5000 ng/ml for paclitaxel,and the correlation coefficient was 0.9980.Paclitaxel released from poly （L-glutamic acid）-alanine-paclitaxel conjugate in rat,dog,monkey and human plasma was higher than that released in acetate buffer and phosphate buffer.Conclusion The method is specific,sensitive and can be applied to the measurement of the concentration of paclitaxel and the evaluation of the stability of poly （L-glutamic acid）-alanine-paclitaxel conjugate.