Qin_2018_Biomed.Chromatogr__e4320

Carboxylesterase and UDP-glucuronosyltransferases mediated metabolism of irinotecan (CPT-11) has long been proposed to be responsible for its anti-tumor activity and toxicity, like delayed-onset diarrhea. However, recent studies failed to gain more comprehensive in vivo and in vitro pharmacokinetic profiles of irinotecan. Herein, we choose rat plasma, human liver microsomes and immortalized HepG2 cell as experimental subjects to describes an sensitive and versatile UHPLC-MS/MS method for simultaneously quantify CPT-11 and its metabolites, including SN-38 and SN-38G. Meanwhile, we have adopted the method to investigate the pharmacokinetic or metabolism behavior of CPT-11 in the above biological samples. Calibration curves for all bio-matrices showed desirable linearity (r(2) >0.99). The intra-day and inter-day precision (RSD, %) were within 15 % and the excellent accuracy (RE, %) was between 2.96% and 14.12%. In addition, the specificity, matrix effect and extraction recovery were all meet the requirements of biological sample analysis. We have successfully applied this method to investigating pharmacokinetic of irinotecan in different biological samples, which mediated by carboxylesterase and UDP-glucuronosyltransferases. And this method could be emplyed in monitoring the metabolic status and clinical efficacy of irinotecan in the future.