Validated method for the determination of platinum from a liposomal source (SPI-77) in human plasma using graphite furnace Zeeman atomic absorption spectrometry

Fresenius J Anal Chem. 2000 Feb;366(3):298-302. doi: 10.1007/s002160050056.

Abstract

A sensitive analytical method based on flameless atomic absorption spectrometry with Zeeman correction has been validated for the quantitative determination in human plasma of platinum originating from cisplatin in a liposomal source, SPI-77. The performance of the method was acceptable over a sample concentration range of 0. 125-1.25 micromol platinum/L and the lower limit of quantification was determined to be 1.25 micromol platinum/L in undiluted clinical samples. The performance data of the assay were investigated using both a calibration curve with carboplatin in plasma ultrafiltrate and diluted human plasma samples spiked with SPI-77. The recoveries, between-day and the within-day precisions of both methods of calibration were not significantly different allowing carboplatin ultrafiltrate calibration standards to be used to quantify platinum derived from SPI-77 in human plasma. Apparently, the liposomal formulation had no significant influence on the determination of platinum. The usefulness of the presented method was demonstrated in a phase I clinical and pharmacokinetic study. In addition, in vitro experiments were carried out to determine the distribution of SPI-77 in blood. The results indicated that platinum from SPI-77 mainly concentrates in plasma and that binding to and/or endocytosis in red blood cells is negligible.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / administration & dosage*
  • Cisplatin / blood*
  • Cisplatin / pharmacokinetics
  • Drug Carriers
  • Humans
  • Liposomes
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrophotometry, Atomic / methods

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • SPI-77, liposomal
  • Cisplatin