Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for simultaneous quantifications of CZ48, lactone-stabilized camptothecin, and camptothecin and their pharmacokinetic and biliary evaluations in rats

Journal of Pharmaceutical and Biomedical Analysis
Yu Jin KimD S-L Chow

Abstract

CZ48, a prodrug of camptothecin (CPT), has a broad spectrum of antitumor activity against various types of human tumors without severe toxicity in preclinical human tumor-xenografted mouse models, which facilitates further preclinical and clinical pharmacokinetic (PK) evaluations of CZ48. In this study, a UHPLC-MS/MS method was developed and validated to simultaneously quantify CZ48 and CPT in rat plasma and bile. Detection was performed using the API 3200 Q Trap triple quadrupole mass spectrometer in a positive ion mode. Chromatographic separation was achieved on Waters ACQUITY UPLC BEH Shield RP18 column with a gradient elution at a flow rate of 0.45 ml/min, using mobile phases of 0.1% acetic acid in water (A) and 0.1% acetic acid in acetonitrile (B). The method was linear at the concentration ranges of 0.98 (LLOQ) -1000 ng/ml of CZ48 and CPT in rat plasma and 3.9 (LLOQ) -1000 ng/ml in bile. Intra- and inter-day accuracy and precision values did not deviate by more than 6.57% and 10.15% for CZ48 and CPT, respectively, in plasma, and 12.09% and 13.48% in bile. Extraction recoveries of CZ48 were 90.18-95.42% from plasma and 86.51 -91.66% from bile. The recoveries of CPT were 91.56-97.06% from plasma and 84.89-89.15% from bile. ...Continue Reading

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