Development of LC-MS/MS Method for Simultaneous Determination of Irinotecan and Its Main Metabolites in Rat Plasma, and Its Application in Pharmacokinetic Studies

作者：Wang, Nanxi; Zhu, Chaoran; Zhai, Xuejia; Zhang, Xinlin; Qin, Yanjie; Lu, Yongning^*

来源：Chromatographia, 2017, 80(1): 77-85.

DOI：10.1007/s10337-016-3207-9

• LC-MS/MS
• Irinotecan
• Metabolites
• Pharmacokinetics
• Personalized medicine

The anticancer agent irinotecan (CPT-11) is widely used in several cancer regimens. However, drug-drug interaction effects and considerable interindividual variability in the pharmacokinetics of CPT-11 and its metabolites have been observed, leading to side effects. To solve these problems and promote CPT-11 treatment, we established and validated a simple, rapid, and sensitive LC-MS/MS method for the simultaneous quantitative determination of CPT-11 and its main metabolites (SN-38, SN-38G, and APC). Protein precipitation with methanol was selected for sample preparation. All separations were performed on an Agilent ZORBAX Eclipse XDB-C18 column (2.1 x 50 mm, 3.5 mu m) under isocratic elution with a mobile phase consisting of acetonitrile and 0.1% formic acid. The mass spectrometer was operated with multiple reaction monitoring in positive ion mode. The method was validated as linear over the concentration ranges 16.9-6760 ng mL(-1) for CPT-11, 2.3-920 ng mL(-1) for SN-38, 2.5-1000 ng mL(-1) for SN-38G, and 1.25-250 ng mL(-1) for APC. The intra- and interbatch precisions and accuracies of the validated method were within acceptable limits (< 15%). This method was successfully applied to a pharmacokinetic study of CPT-11 and its main metabolites in rats.

• 出版日期2017-1
• 单位华中科技大学