摘要
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/z 299.4。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。
A sensitive and selective method has been developed and validated for the quantitation of paclitaxel in human plasma by liquid chromatography-electrospray 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.
