A full validated hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the quantification of oxaliplatin in human plasma ultrafiltrates

J Pharm Biomed Anal. 2012 Dec:71:99-103. doi: 10.1016/j.jpba.2012.08.010. Epub 2012 Aug 17.

Abstract

Oxaliplatin is a platinum agent that is used for treatment of colorectal cancer. A sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the quantification of oxaliplatin was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin as an internal standard and further diluted with acetonitrile. Chromatographic separation of oxaliplatin and the internal standard was achieved with a column modified with phosphorylcholine and an isocratic mobile phase (acetonitrile/water/acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. The lower limit of quantification for oxaliplatin was 25ng/mL. The linearity range of the method was from 25 to 5000ng/mL. The intra-day precision and inter-day precision (RSD) ranged from 0.8 to 6.1%, and the accuracy (RE) was within ±4.5%. The extraction recoveries from human plasma ultrafiltrates were 83.6-91.6%, and ion suppression caused by matrix components was 86.7-88.5% at three different levels, respectively. This method was applied to a clinical pharmacokinetic study of oxaliplatin in a cancer patient. The maximum concentration of colorectal cancer patient administered oxaliplatin was 1650ng/mL.

MeSH terms

  • Acetonitriles / chemistry
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / pharmacokinetics
  • Chromatography, Liquid / methods*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Organoplatinum Compounds / blood*
  • Organoplatinum Compounds / pharmacokinetics
  • Oxaliplatin
  • Phosphorylcholine / chemistry
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Ultrafiltration

Substances

  • Acetonitriles
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Phosphorylcholine
  • acetonitrile