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Rapid LC–MS/MS method for quantification of vinorelbine and 4 ‐O‐ deacetylvinorelbine in human whole blood suitable to monitoring oral metronomic anticancer therapy
Author(s) -
Corona Giuseppe,
Gusella Milena,
Gaspardo Anna,
Miolo Gianmaria,
Bertolaso Laura,
Pezzolo Elisa,
Pasini Felice,
Steffan Agostino,
Caruso Donatella
Publication year - 2018
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4282
Subject(s) - vinorelbine , chromatography , protein precipitation , therapeutic drug monitoring , pharmacokinetics , analyte , whole blood , chemistry , selected reaction monitoring , active metabolite , pharmacology , mass spectrometry , tandem mass spectrometry , medicine , chemotherapy , cisplatin
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 C 18 , 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 R 2 ≥ 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.