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

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Abstract

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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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (grants 81403012 and 81473287).

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Authors and Affiliations

  1. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

    Nanxi Wang, Chaoran Zhu, Xuejia Zhai, Xinlin Zhang, Yanjie Qin & Yongning Lu

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  1. Nanxi Wang
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  2. Chaoran Zhu
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  3. Xuejia Zhai
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  4. Xinlin Zhang
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  5. Yanjie Qin
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  6. Yongning Lu
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Correspondence to Yongning Lu.

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Wang, N., Zhu, C., Zhai, X. et al. Development of LC–MS/MS Method for Simultaneous Determination of Irinotecan and Its Main Metabolites in Rat Plasma, and Its Application in Pharmacokinetic Studies. Chromatographia 80, 77–85 (2017). https://doi.org/10.1007/s10337-016-3207-9

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  • DOI: https://doi.org/10.1007/s10337-016-3207-9

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