A validated high-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of irinotecan and two major metabolites in rat plasma: Application for the pharmacokinetics study

A high-performance liquid chromatography-tandem mass spectrometry method has been developed for the determination of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN38), and SN38 glucuronide (SN38G) in rat plasma in the present study. The analytes were separated on a C18 column and a triple-quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Irinotecan, SN38 and SN38G could be well retained in the C18 column after optimization of mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was above 90% and the matrix effect could be negligible. The method was linear over the concentration ranges of 3.46-3458.8 ng/mL for irinotecan, 2.53-2530.0 ng/mL for SN38 and 2.5-2500.0 ng/mL for SN38G. The precision and accuracy was within the acceptable limits. The simple and convenient method was validated and successfully applied to support the pharmacokinetic study and elucidate the mechanism of irinotecan-induced diarrhea after irinotecan was intravenously injected to the Sprague-Dawley rats.