Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Sumit BasuMing Hu

Abstract

The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases. Triple quadruple mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode were employed to perform mass analysis. The results showed that the linear response range of irinotecan and SN-38 in plasma, feces, liver and kidney is 4.88-10000 nM, 39-5000 nM, 48.8-6250 nM and 48.8-6250 nM, respectively (R(2)>0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25-2000 nM, 4.88-1250 nM, 9.8-1250 nM and 9.8-1250 nM in plasma, feces, liver and kidney homogenates, respectively. The lower limit of detection (LLOD) of irinotecan, SN-38 and SN-38 glucuronide was determined to be less than 25 nM in all bio-matrices as well as tissue homogena...Continue Reading

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Citations

Jun 1, 2017·The Analyst·Nicolas GuichardSandrine Fleury-Souverain
Feb 7, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Abdul Naveed ShaikMirjam N Trame
Jun 23, 2018·Current Medicinal Chemistry·Roberta Zilles HahnRafael Linden
Sep 24, 2019·Expert Review of Clinical Pharmacology·Aleksandra Tarasiuk, Jakub Fichna
Jan 28, 2020·PLoS Computational Biology·Roger J W HillAnnabelle Ballesta
Apr 2, 2020·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Xia GongLingzhi Gong

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