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

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 C , 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 ≥ 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 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.

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods for the therapeutic drug monitoring of cytotoxic anticancer drugs: An update

“…Nevertheless, in this review, vorinostat and its glucuronide metabolite for example have been quantified in the same method using the same daughter ion [107] and the method still passed validation. This also applies to another example with vinorelbine and its deacetyl metabolite, also successfully validated [88].…”

“…In some cases, determination in whole blood is more appropriate than in plasma. This is the case for vinorelbine, which binds primarily to platelets and blood cells and is therefore quantified in whole blood [88,90,121], with some exceptions where quantification in plasma may be more practical as part of a multiplexed assay for example [77]. For the widely investigated case of thiopurines, the assay is carried out in red blood cell (RBCs).…”

Electroanalytical Investigation of Cancer Chemotherapy Drug Vinorelbine On Disposable Pencil Graphite Electrode in Surfactant Media by Voltametric Method

“…According to the literature review, it has been seen that liquid chromatography (LC) has been the most widely used method in the last two decades for the determination of Vinca alkaloids in general, Vinorelbine in particular, from different media (pharmaceutical forms, environmental samples and biological samples such as urine, blood, tissue). Mass spectrometry (MS) is preferred as a detection system especially for pharmacokinetic studies [4][5][6][7][8]. Although LC has high…”