A rapid, simple and reliable HPLC-triple quadrupole tandem mass spectrometer method for a simultaneous quantification of irinotecan and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN38) in mouse plasma.

A simple, fast and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method (HPLC-MS/MS method) was developed, validated and used for the simultaneous quantification of irinotecan and 7-ethyl-10-hydroxycamptothecin (SN38) in heparinized mouse plasma. Camptothecin was used as the internal standard. A single-step protein precipitation without evaporation and reconstitution steps was adopted as sample processing method. Our bioanalytical method was validated in compliance with the guidelines from the European Medicines Agency. The lower limit of quantification for both irinotecan and SN38 was 5ng/mL. The calibration curves for both analytes fitted to a 1/x2 weighted linear regression model and ranged from 5 to 1000ng/mL. The intra-run and inter-run precisions were within 8.6%, and the intra-run and inter-run accuracies were within 96.4-103.9%. Our validated bioanalytical method was successfully applied to the pharmacokinetic study in mice, in which 4mg/kg irinotecan was intraperitoneally injected. Copyright (c) 2014 John Wiley & Sons, Ltd.