Determination of irinotecan, SN-38 and SN-38 glucuronide using HPLC/MS/MS: Application in a clinical pharmacokinetic and personalized medicine in colorectal cancer patients

J Clin Lab Anal. 2018 Jan;32(1):e22217. doi: 10.1002/jcla.22217. Epub 2017 Apr 10.

Abstract

Background: Irinotecan (CPT-11) is chemotherapy used mainly in the metastatic colorectal cancer. The purpose of this study was to develop and validate the LC-MS/MS for the simultaneous determination of CPT-11, SN-38, and SN-38G.

Methods: A 100 μL of plasma was prepared after protein precipitation and analyzed on a C18 column using 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile as mobile phases. The mass spectrometer worked with multiple reaction monitoring (MRM) in positive scan mode. The standard curves were linear on a concentration range of 5-10 000 ng/mL for CPT-11, 5-1000 ng/mL for SN-38, and 8-1000 ng/mL for SN-38G.

Results: In this assay, the intra and interday precision consisted of ≤9.11% and ≤11.29% for CPT-11, ≤8.70% and 8.31% for SN-38, and ≤9.90 and 9.64% for SN-38G.

Conclusion: This method was successfully used to quantify CPT-11, SN-38, and SN-38G and applied to a pharmacokinetic study.

Keywords: CPT-11; LC-MS/MS; SN-38; SN-38G; colorectal cancer.

MeSH terms

  • Antineoplastic Agents, Phytogenic / blood*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Camptothecin / chemistry
  • Camptothecin / pharmacokinetics
  • Camptothecin / therapeutic use
  • Chromatography, High Pressure Liquid / methods*
  • Colorectal Neoplasms / drug therapy*
  • Drug Monitoring
  • Glucuronides / blood*
  • Glucuronides / chemistry
  • Glucuronides / pharmacokinetics
  • Humans
  • Irinotecan
  • Precision Medicine
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*

Substances

  • 7-ethyl-10-hydroxycamptothecin glucuronide
  • Antineoplastic Agents, Phytogenic
  • Glucuronides
  • Irinotecan
  • Camptothecin