Determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin in human plasma by sensitive high-performance liquid chromatography with fluorescence detection

J Chromatogr B Biomed Sci Appl. 1997 Jul 4;694(2):435-41. doi: 10.1016/s0378-4347(97)00117-5.

Abstract

Two sensitive reversed-phase high-performance liquid chromatographic fluorescence methods, with simple sample handling at the site of the patient, are described for the determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin (9AC). For 9AC lactone, the sample preparation was a liquid-liquid extraction with acetonitrile-n-butyl chloride (1:4, v/v), whereas the sample preparation for 9AC total (lactone plus carboxylate) was a simple deproteinization with 5% perchloric acid-methanol (1:1, v/v), which results in the conversion of the carboxylate into the lactone form. The lower limits of quantitation were 50 pg/ml and 100 pg/ml for 9AC lactone and 9AC total, respectively. The within-run precisions at four tested concentrations were < or = 6.3% for 9AC lactone and < or = 5.3% for 9AC total. The between-run precisions were < or = 8.9% and < or = 5.6%, respectively. The assays were developed to enable pharmacological analysis of 9AC in a bioavailability and oral phase I study in patients with solid tumors.

MeSH terms

  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Camptothecin / chemistry
  • Camptothecin / therapeutic use
  • Carboxylic Acids / blood*
  • Carboxylic Acids / chemistry
  • Chromatography, High Pressure Liquid
  • Humans
  • Hydrogen-Ion Concentration
  • Lactones / blood*
  • Lactones / chemistry
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Lactones
  • 9-aminocamptothecin
  • Camptothecin