Development of LC–MS/MS Method for Simultaneous Determination of Irinotecan and Its Main Metabolites in Rat Plasma, and Its Application in Pharmacokinetic Studies
2017
Wang, Nanxi | Zhu, Chaoran | Zhai, Xuejia | Zhang, Xinlin | Qin, Yanjie | Lu, Yongning
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 × 50 mm, 3.5 μm) 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.
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