Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Feb 15:917-918:18-23. doi: 10.1016/j.jchromb.2012.11.024. Epub 2012 Dec 3.

Abstract

Carboplatin is a platinum agent that is used for treatment of non-small-cell lung cancer and ovarian cancer. A sensitive and selective analytical method for the quantification of carboplatin in human plasma ultrafiltrates using liquid chromatography-tandem mass spectrometry was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin-d4 as an internal standard and were further diluted with acetonitrile. Chromatographic separation was performed on a Accucore HILIC (50mm×2.1mm i.d., 2.6μm) column using mobile phase (acetonitrile-water-acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. Detection was performed on electrospray ionization triple quadrupole tandem mass spectrometer using low-energy collision induced dissociation (CID-MS/MS) analysis operating in the selected reaction monitoring (SRM) scan mode. The lower limit of quantification for carboplatin was 0.025μg/mL. This method covered a linearity range of 0.025-50μg/mL. The intra-day precision and inter-day precision (R.S.D.) ranged from 1.5 to 4.3%, and the accuracy (R.E.) was within ±2.9%. The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient.

MeSH terms

  • Carboplatin / blood*
  • Carboplatin / isolation & purification
  • Carboplatin / pharmacokinetics
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Linear Models
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Ultrafiltration

Substances

  • Carboplatin