Quantification of irinotecan, SN38, and SN38G in human and porcine plasma by ultra high-performance liquid chromatography-tandem mass spectrometry and its application to hepatic chemoembolization

Xiaohong Chen, Cody J. Peer, Raul Alfaro, Tian Tian, Shawn D. Spencer, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

An analytical method was developed and validated for the quantitative determination of irinotecan, its active metabolite SN38, and glucuronidated SN38 (SN38-G) in both porcine and human plasma. Calibration curves were linear within the concentration range of 0.5-100. ng/mL for SN38 and SN38-G, and 5-1000. ng/mL for irinotecan. Sample pretreatment involved solid-phase extraction of 0.1. mL aliquots of plasma. Irinotecan, SN38, SN38-G, and the internal standards, irinotecan-d10, tolbutamide, and camptothecin, respectively, were separated on a Waters ACQUITY UPLC™ BEH RP18 column (2.1 mm × 50 mm, 1.7 μm), using a mobile phase composed of methanol and 0.1% formic acid. Accuracy of quality control samples in human plasma ranged from 98.5 to 110.3%, 99.5 to 101.7% and 96.2 to 98.9% for irinotecan, SN38, and SN38-G, respectively. Precision of the three analytes in the same order ranged from 0.8 to 2.8%, 2.4 to 5.7%, and 2.4 to 2.8%. All three analytes proved stable in plasma through four freeze/thaw cycles, as well as through 6. h in whole blood at room temperature. The method was likewise validated in porcine plasma with comparable accuracies and precisions also within the generally acceptable range. The validated method was applied to both preclinical and clinical trials involving hepatic chemoembolization of irinotecan drug-eluting beads to study the pharmacokinetics of the three analytes.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume62
DOIs
StatePublished - 25 Mar 2012
Externally publishedYes

Keywords

  • Camptothecin
  • Irinotecan
  • Mass spectrometry
  • SN38
  • Ultra-high performance liquid chromatography

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