A sensitive and selective method has been developed and validated for the quantitation of paclitaxel in human plasma by liquid chromatography-eleetrospray ionization mass spectrometry (LC-ESI-MS).Paclitaxel and norethindrone (used as internal standard,I.S.) were extracted from human plasma by a one-step liquid-liquid extraction with t-butyl methyl ether.Separation on a Zorbax SB-C18 column (100 mm×2.1 mm,3.5 μm,Agilent) was achieved by gradient elution with methanol and 0.2 mmol/L ammonium formate containing 0.1％ formic acid.The selected-ion monitoring (SIM) targeted ions of [M+Na]+ at m/z 876.5 for paclitaxel and [M+H](+) at m/z 299.4 for I.S.The assay was validated in the range of 1.0-400 ng/mL (r＞0.998) with LLOQ of 1.0 ng/mL.Intra- and inter-day precisions were all less than 9.0％,with accuracies of±6.8％.The method was successfully applied to evaluate the pharmacokinetics of paclitaxel liposome for injection in patients.%建立了一种灵敏度高、特异性好的高效液相色谱-电喷雾质谱法(LC-ESI-MS)测定人血浆中紫杉醇浓度的方法.采用一步液液萃取法进行血浆样品预处理,提取液为甲基叔丁基醚,内标选用炔诺酮.色谱柱为Zorbax SB-C18柱(100 mm×2.1 mm,3.5 μm,Agilent),流动相为甲醇-0.2 mmol/L甲酸铵缓冲盐溶液(包含0.1％甲酸),采用梯度洗脱.选择离子监测(SIM)的目标离子为紫杉醇的[M+Na]+ m/z 876.5和内标的[M+H]+m/z299.4.方法学验证表明线性范围是1.0-400 ng/mL(r＞0.998),最低定量限为1.0 ng/mL,方法的批内和批间精密度都小于9.0％,准确度在6 8％以内.此方法已成功应用于紫杉醇脂质体注射液在患者体内的药动学研究.
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