Sensitive determination of irinotecan (CPT-11) and its active metabolitel SN-38 in human serum using liquid chromatography-electrospray mass spectrometry

摘要

A couple of sensitive and accurate liquid chromatography-electrospray mass spectrometry (LC-ES-MS) methods for the determination of the total forms of irinotecan and its active metabolite SN-38 in human serum, using the same chomatographic and detection conditions, is presented. Both used camptothecin as internal standard (I.S.).The sample pretreatment for irinotecn involved a simple protein precipitation with acetonitrile, whereas a liquid-liuqid extraction was necessary for SN-38. A Symmetry C_(18),3.5 #mu#m (150×1 mm I.D) reversed-phase column was used for the chromatographic separation, together with a gradient elution of acetonitrile in 5 mM ammonium formate buffer (pH 3) as mobile phasw. After ionisation in the pneumatically-assisted electrospray source and in-soure collision induced dissociation, acquisition was performed in the selected ion monitoring mode. Recoveries were 69 and 47% on average, detection limits 2.5 and 0.25 ng/ml and quantitation limits 10 and 0.5 ng/ml for irinotecan and SN-38, respectively. Reproducibility was good and the method was linear from limits of quantitation up to 10 000 ng/ml for irinotecan, and up to 100 ng/ml for SN-38. This sensitive and highly specific method is suitable both for pharmacokinetic studies and routine therapeutic drug monitoring.