Optimization of LC method for the quantification of doxorubicin in plasma and urine samples in view of pharmacokinetic, biomedical and drug monitoring therapy studies

J Pharm Biomed Anal. 2018 Sep 5:158:376-385. doi: 10.1016/j.jpba.2018.06.031. Epub 2018 Jun 19.

Abstract

A simple, rapid, reliable and sensitive method based on liquid chromatography with fluorescence detection (LC-FL) for the quantification of doxorubicin (DOX) in human plasma and urine samples was developed. The assay was carried out after the solid-phase extraction procedure (SPE) with hydrophilic-lipophilic balance (HLB) cartridges, and with daunorubicin hydrochloride (DAU) used as the internal standard. Chromatographic separation was performed on a Discovery HS C18 column in isocratic elution mode, and the detection of the analytes set at excitation and emission wavelengths of 487 and 555 nm, respectively. The developed LC-FL method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification for DOX were 0.5 and 1 ng/mL in both biological fluids, respectively. Linearity was confirmed in the range of 1-1000 ng/mL and 0.001-25 μg/mL in plasma and urine samples, respectively, with a correlation coefficient greater than 0.9994. The proposed LC-FL method is selective, precise and accurate, and has been successfully applied for drug monitoring in pediatric cancer patients treated with DOX as a component of OEPA (Oncovin (Vincristine)-Etoposide-Prednisone-Adriamycin) and IOA (Ifosfamide-Oncovin-Adriamycin) chemotherapeutic schemes. Moreover, real exposure of hospital personnel to the anthracycline drugs in plasma and urine was evaluated in clinical practice.

Keywords: Doxorubicin; Drug monitoring; Fluorescence detection; Liquid chromatography; Plasma; Urine.

Publication types

  • Validation Study

MeSH terms

  • Adolescent
  • Antibiotics, Antineoplastic / analysis*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibiotics, Antineoplastic / toxicity
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • Daunorubicin / analysis
  • Doxorubicin / analysis*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Drug Monitoring / methods*
  • Etoposide / therapeutic use
  • Fluorescence
  • Humans
  • Limit of Detection
  • Male
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / urine
  • Occupational Exposure / adverse effects
  • Personnel, Hospital
  • Prednisone / therapeutic use
  • Reproducibility of Results
  • Solid Phase Extraction
  • Vincristine / therapeutic use

Substances

  • Antibiotics, Antineoplastic
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Prednisone
  • Daunorubicin

Supplementary concepts

  • AOPE protocol