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

doi:10.1002/bmc.4282

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

Biomed Chromatogr. 2018 May 10:e4282. doi: 10.1002/bmc.4282. Online ahead of print.

Authors

Giuseppe Corona¹, Milena Gusella², Anna Gaspardo³, Gianmaria Miolo⁴, Laura Bertolaso², Elisa Pezzolo², Felice Pasini⁵, Agostino Steffan¹, Donatella Caruso³

Affiliations

¹ Immunopathology and Cancer Biomarkers Unit, Translational Research Department, IRCCS National Cancer Institute, Aviano, Italy.
² Oncology Department, Santa Maria della Misericordia Hospital, Rovigo, Italy.
³ Pharmacological and Biomolecular Science Department, University of Milan Milan, Italy.
⁴ Medical and Preventive Oncology Unit, IRCCS National Cancer Institute, Aviano, Italy.
⁵ Medical Oncology Unit, Piero Pederzoli Hospital, Peschiera del Garda, Italy.

PMID: 29749011
DOI: 10.1002/bmc.4282

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 C^Trough 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.

Keywords: 4-O-deacetylvinorelbine; LC/MS/MS; cancer; metronomic; vinorelbine.