The implementation of therapeutic drug monitoring in the routine clinical practice in oncology is mainly limited by the lack of therapeutic indexes for the majority of the anticancer drugs, and by the absence of suitable analytical tools, which can accurately quantify in real time the concentration of the administered drugs and their relevant metabolites in biological fluids. In this work, a simple and efficient fluorimetric determination of SN-38, the active metabolite of the anticancer drug irinotecan, was developed and applied to human plasma samples. The intrinsic fluorescence of SN-38 allowed its quantification in the range 10–500 ng mL −1 with a LOQ of 5.0 ng mL −1 and a LOD of 1.5 ng mL −1 . Low interferences due to main metabolites of irinotecan and comedications, commonly associated with administration of irinotecan, were observed. A validation study, according to FDA and EMA guidelines for bioanalytical method validation, was carried out and, finally, blind samples were analyzed in parallel with a HPLC-MS method obtaining an excellent agreement between the two techniques.

Practical fluorimetric assay for the detection of anticancer drug SN-38 in human plasma

Polo F.
Writing – Original Draft Preparation
;
2018

Abstract

The implementation of therapeutic drug monitoring in the routine clinical practice in oncology is mainly limited by the lack of therapeutic indexes for the majority of the anticancer drugs, and by the absence of suitable analytical tools, which can accurately quantify in real time the concentration of the administered drugs and their relevant metabolites in biological fluids. In this work, a simple and efficient fluorimetric determination of SN-38, the active metabolite of the anticancer drug irinotecan, was developed and applied to human plasma samples. The intrinsic fluorescence of SN-38 allowed its quantification in the range 10–500 ng mL −1 with a LOQ of 5.0 ng mL −1 and a LOD of 1.5 ng mL −1 . Low interferences due to main metabolites of irinotecan and comedications, commonly associated with administration of irinotecan, were observed. A validation study, according to FDA and EMA guidelines for bioanalytical method validation, was carried out and, finally, blind samples were analyzed in parallel with a HPLC-MS method obtaining an excellent agreement between the two techniques.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0731708518305417-main.pdf

non disponibili

Descrizione: Articolo principale
Tipologia: Versione dell'editore
Licenza: Accesso chiuso-personale
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF   Visualizza/Apri
1-s2.0-S0731708518305417-mmc1.pdf

non disponibili

Descrizione: Supporting information
Tipologia: Versione dell'editore
Licenza: Accesso chiuso-personale
Dimensione 767.19 kB
Formato Adobe PDF
767.19 kB Adobe PDF   Visualizza/Apri

I documenti in ARCA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10278/3718226
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact