A simple dried blood spot method for clinical pharmacological analyses of etoposide in cancer patients using liquid chromatography and fluorescence detection

作者：Kukec Renata Rezonja; Grabnar Iztok; Mrhar Ales; Lipovec Nanca Cebron; Cufer Tanja; Vovk Tomaz^*

来源：Clinica Chimica Acta, 2016, 452: 99-105.

DOI：10.1016/j.cca.2015.10.026

• Etoposide
• Dried blood spot
• Lung cancer
• Therapeutic drug monitoring

Background: Therapeutic drug monitoring of etoposide is not part of the routine clinical practice, however, measuring etoposide plasma concentration may be useful to prevent chemotherapy related adverse drug reactions. This paper describes the development and validation of a dried blood spot (DBS) assay for the determination of etoposide in blood samples of lung cancer patients.
Methods: The whole blood spot was cut out of the DBS card followed by sonication assisted liquid drug extraction. Extraction solution was evaporated and re-dissolved. A high-performance-liquid-chromatography method with fluorimetric detection ( lambda(ex) = 230 lambda(em); = 330 nm) was used.
Results: Method met the validation criteria in terms of selectivity, linearity (0.5-20.0 mu g/mL), accuracy (>= 96.1%), precision (<= 10.1%) and stability (long term 4 weeks at room temperature and 40 degrees C). Haematocrit did not influence DBS etoposide concentration. Good correlation between measured plasma and DBS concentrations was observed. The equation considering only haematocrit value was used for conversion of DBS to plasma concentration.
Conclusions: DBS sampling method showed comparable results to plasma samples. Therefore, it can be concluded that the developed and validated DBS method, which is more patient-friendly and requires less sample handling, is a reliable alternative to conventional plasma methods for measuring etoposide concentration in clinical pharmacological analyses.

• 出版日期2016-1-15