Rapid LC–MS/MS method for quantification of vinorelbine and 4-O-deacetylvinorelbine in human whole blood suitable to monitoring oral metronomic anticancer therapy

Giuseppe Corona, Milena Gusella, Anna Gaspardo, Gianmaria Miolo, Laura Bertolaso, Elisa Pezzolo, Felice Pasini, Agostino Steffan, Donatella Caruso

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A rapid and sensitive LC–MS/MS method for therapeutic drug monitoring oral vinorelbine (VRL) metronomic anticancer chemotherapy has been developed and validated. Analysis of VRL and its main active metabolite 4-O-deacetylvinorelbine (M1) was performed in whole blood matrix. Both analytes were extracted by protein precipitation and separated on an Onyx monolith C18, 50 × 2 mm column then quantified by positive electrospray ionization and multiple reaction monitoring mode. The LLOQ was 0.05 ng/mL for both VRL and M1. Linearity was up to 25ng/mL with R2 ≥ 0.994. The intra- and inter-assay precisions were ≤ 11.6 and ≤ 10.4% while the ranges of accuracy were [−8.7%; 10.3%] and [−10.0; 7.4%] for VRL and M1, respectively. The clinical suitability of the method has been proved by the determination of the CTrough blood concentrations of VRL and M1 in 64 nonsmall cell lung cancer elderly patients. The analytical performance of the assay was suitable for pharmacokinetic monitoring of VRL and M1, allowing the personalization of the VRL metronomic treatments.

Original languageEnglish
Article numbere4282
JournalBiomedical Chromatography
Volume32
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Blood
Monitoring
Assays
Therapeutics
Electrospray ionization
Pharmacokinetics
Chemotherapy
Drug Monitoring
Metabolites
4-O-deacetyl vinorelbine
vinorelbine
Non-Small Cell Lung Carcinoma
Cells
Drug Therapy
Pharmaceutical Preparations
Proteins

Keywords

  • 4-O-deacetylvinorelbine
  • cancer
  • LC/MS/MS
  • metronomic
  • vinorelbine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Rapid LC–MS/MS method for quantification of vinorelbine and 4-O-deacetylvinorelbine in human whole blood suitable to monitoring oral metronomic anticancer therapy. / Corona, Giuseppe; Gusella, Milena; Gaspardo, Anna; Miolo, Gianmaria; Bertolaso, Laura; Pezzolo, Elisa; Pasini, Felice; Steffan, Agostino; Caruso, Donatella.

In: Biomedical Chromatography, Vol. 32, No. 9, e4282, 01.09.2018.

Research output: Contribution to journalArticle

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abstract = "A rapid and sensitive LC–MS/MS method for therapeutic drug monitoring oral vinorelbine (VRL) metronomic anticancer chemotherapy has been developed and validated. Analysis of VRL and its main active metabolite 4-O-deacetylvinorelbine (M1) was performed in whole blood matrix. Both analytes were extracted by protein precipitation and separated on an Onyx monolith C18, 50 × 2 mm column then quantified by positive electrospray ionization and multiple reaction monitoring mode. The LLOQ was 0.05 ng/mL for both VRL and M1. Linearity was up to 25ng/mL with R2 ≥ 0.994. The intra- and inter-assay precisions were ≤ 11.6 and ≤ 10.4{\%} while the ranges of accuracy were [−8.7{\%}; 10.3{\%}] and [−10.0; 7.4{\%}] for VRL and M1, respectively. The clinical suitability of the method has been proved by the determination of the CTrough blood concentrations of VRL and M1 in 64 nonsmall cell lung cancer elderly patients. The analytical performance of the assay was suitable for pharmacokinetic monitoring of VRL and M1, allowing the personalization of the VRL metronomic treatments.",
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AU - Gaspardo, Anna

AU - Miolo, Gianmaria

AU - Bertolaso, Laura

AU - Pezzolo, Elisa

AU - Pasini, Felice

AU - Steffan, Agostino

AU - Caruso, Donatella

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