人血清中伊立替康的液质联用测定方法

Determination of irinotecan in human serum by liquid chromatography-electrospray mass spectrometry

目的 建立高效液相 质谱联用法 (LC MS)测定人血清中伊立替康 (CPT 11)的浓度。方法 液相 :采用WatersSymmetryC18色谱柱 (2 . 1mm× 15 0mm ,5 μm) ;流动相 :甲醇 -5mmol·L-1甲酸铵缓冲液 (38∶6 2 ) ;流速 :0 . 2mL·min-1。质谱 :电喷雾电离源(ESI+ ) ,选择性离子监测 (SIR)质荷比 (m/z)为 5. 87。以盐酸洛贝林为内标 ,采用乙腈沉淀蛋白 ,上清液经酸化后进样分析。结果 本方法在 10～ 10 0 0 0ng·mL-1内线性良好 ,相关系数r=0 996. 7(n =7)。高、中、低浓度质控样品的批内RSD均在 2 . 70 %～ 4 5. 8% ,批间RSD均在 2 . 74 %～ 5 . 82 % ,方法学回收率为 98. 2 1%～ 110 . 4 9% ,最低检测浓度为 0 . 2ng·mL-1。结论 本方法灵敏度高 ,操作简便易行 ,完全能满足体内低药物浓度的测定 ,可用于该药临床药物动力学特性的研究。

OBJECTIVE: To develop a liquid chromatography-electrospray mass spectrometry (LC-MS) method for the determination of irinotecan(CPT-11) in human serum. METHODS: A Symmetry C18 column (150 mm × 2.1 mm, 5 μm) was used and the mobile phase consisted of methanol:5 mmol&middotL -1 ammonium formate buffer (38:62) at the flow rate of 0.2 mL&middotmin-1. Acquisition was performed with the selected ion monitoring mode (SIR, m/z 587) after the ionization in the electrospray source. The sample treatment for irinotecan involved a simple protein precipitation with acetonitrile, and lobeline worked as the internal standard. The supernatant was acidified and directly injected into the HPLC system. RESULTS: The method was linear over the range of 10-10 000 ng&middotmL-1 (r = 0.996 7, n = 7). The inter-and intra-run validations were between 2.70%-5.82%. The mean recoverys were 98.21%, 110.49% and 109.84% for the low, middle and high concentrations of check samples, respectively. The limit of detection was 0.2 ng&middotmL-1. CONCLUSION: The method appeared to be sensitive, specific and simple. It is suitable for the clinical pharmacokinetics study.