title: A simple dried blood spot method for clinical pharmacological analyses of etoposide in cancer patients using liquid chromatography and fluorescence detection.
abstract: 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 ( λex=230nm; λem=330nm) was used.
  
  
  RESULTS
  Method met the validation criteria in terms of selectivity, linearity (0.5-20.0μg/mL), accuracy (≥96.1%), precision (≤10.1%) and stability (long term 4weeks at room temperature and 40°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.
authors.affiliation: Krka, d.d., Novo mesto, Slovenia; University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Renata
authors.initials: R
authors.lastname: Režonja Kukec
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Aleš
authors.initials: A
authors.lastname: Mrhar
authors.affiliation: University Clinic Golnik, Golnik, Slovenia.
authors.forename: Nanča
authors.initials: N
authors.lastname: Čebron Lipovec
authors.affiliation: University Clinic Golnik, Golnik, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Čufer
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia. Electronic address: tomaz.vovk@ffa.uni-lj.si.
authors.forename: Tomaž
authors.initials: T
authors.lastname: Vovk
mesh_terms: D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing; D005047:Etoposide / Q000097:blood* / Q000737:chemistry; D005453:Fluorescence; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood*; D055752:Small Cell Lung Carcinoma / Q000097:blood*
chemical_list: D005047:Etoposide
keywords: Dried blood spot; Etoposide; Lung cancer; Therapeutic drug monitoring