Hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the determination of intact oxaliplatin in cells: validated and applied in colon cancer HCT-116 cell line

J Pharm Biomed Anal. 2018 Jun 5:155:7-14. doi: 10.1016/j.jpba.2018.03.045. Epub 2018 Mar 22.

Abstract

Oxaliplatin is a platinum compound that is frequently prescribed for the chemotherapeutic treatment of colorectal cancer. In tumor cells, cellular uptake is the first step of oxaliplatin action. Cellular accumulation of oxaliplatin is considered to play an important role in anti-cancer efficacy. However, limited information about cellular accumulation of intact oxaliplatin is available. In this study, a sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach for the quantification of oxaliplatin in cells was developed and validated. The method allowed for a rapid and simple determination of intact oxaliplatin in cell lysate. The retention time of oxaliplatin was 3.04 min, which was achieved by applying a chromatographic gradient elution of 5 min. The lower limit of quantification (LLOQ) was 2 ng/mL and the analytical range of oxaliplatin was linear between 2-200 ng/mL. The intra-day precision and inter-day precision (RSD (relative standard deviation)) ranged from 0.52 to 7.89%, and the accuracy (RE (relative error)) was within ± 4.5%. Matrix effects and recovery were acceptable. The method was successfully used for the determination of intact oxaliplatin uptake by HCT-116 colon cancer cells. Thus, our findings may prospectively support a celluar pharmacokinetic study and low concentration measurement of intact oxaliplatin in the clinic.

Keywords: Cellular; HCT-116; HILIC-MS/MS; Oxaliplatin.

MeSH terms

  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid / methods
  • Colonic Neoplasms / chemistry*
  • HCT116 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Organoplatinum Compounds / chemistry*
  • Oxaliplatin
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods

Substances

  • Organoplatinum Compounds
  • Oxaliplatin