Sensitive determination of irinotecan (CPT-11) and its active metabolite SN-38 in human serum using liquid chromatography-electrospray mass spectrometry
Sensitive determination of irinotecan (CPT-11) and its active metabolite SN-38 in human serum using liquid chromatography-electrospray mass spectrometry
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DOI：
10.1016/s0378-4347(99)00452-1
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发表时间：
1999-12-24
期刊：
影响因子：
--
通讯作者：
Lachâtre, G
中科院分区：
文献类型：
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作者：
Ragot, S;Marquet, P;Lachâtre, G
一对灵敏准确的液相色谱-电喷雾质谱联用技术本文采用液相色谱-电喷雾串联质谱（LC-ES-MS）法，以喜树碱为内标，采用相同的色谱和检测条件，测定人血清中伊立替康及其活性代谢产物SN-38的总形式（I.S），伊立替康的样品预处理包括使用乙腈进行简单的蛋白质沉淀，而SN-38需要进行液-液萃取。A Symmetry C-18，3.5 μ m（150X1 mm I.D.）使用反相柱进行色谱分离，同时使用乙腈在5 mM甲酸铵缓冲液（pH 3）中的梯度洗脱作为移动的相。在电喷雾辅助源和源内碰撞诱导解离中电离后，以所选离子监测模式进行采集。伊立替康和SN-38的平均回收率分别为69%和47%，检测限分别为2.5和0.25 ng/ml，定量限分别为10和0.5 ng/ml。重现性良好，该方法在伊立替康高达10 000 ng/ml和SN-38高达100 ng/ml的定量限范围内呈线性。该方法灵敏度高，特异性强，适用于药代动力学研究和常规治疗药物监测。(C)1999年Elsevier Science BN。All rights reserved.
A couple of sensitive and accurate liquid chromatography-electrospray mass spectrometry (LC-ES-MS) methods for the determination of the total forms of irinotecan and its active metabolite SN-38 in human serum, using the same chromatographic and detection conditions, is presented, Both used camptothecin as internal standard (I.S,), The sample pretreatment for irinotecan involved a simple protein precipitation with acetonitrile, whereas a liquid-liquid extraction was necessary for SN-38. A Symmetry C-18, 3.5 mu m (150X1 mm I.D.) reversed-phase column was used for the chromatographic separation, together with a gradient elution of acetonitrile in 5 mM ammonium formate buffer (pH 3) as mobile phase. After ionisation in the pneumatically-assisted electrospray source and in-source collision induced dissociation, acquisition was performed in the selected ion monitoring mode. Recoveries were 69 and 47% on average, detection Limits 2.5 and 0.25 ng/ml and quantitation limits 10 and 0.5 ng/ml for irinotecan and SN-38, respectively. Reproducibility was good and the method was linear from limits of quantitation up to 10 000 ng/ml for irinotecan, and up to 100 ng/ml for SN-38. This sensitive and highly specific method is suitable both for pharmacokinetic studies and routine therapeutic drug monitoring. (C) 1999 Elsevier Science BN. All rights reserved.