New sensitive liquid chromatography method coupled with tandem mass spectrometric detection for the clinical analysis of vinorelbine and its metabolites in blood, plasma, urine and faeces

A new sensitive and specific liquid chromatographic method coupled with tan dem mass spectrometric detection was set up and validated for the simultane ous quantitation of vinorelbine, its main metabolite, 4-O-deacetylvinorelbi ne and two other minor metabolites, 20 ' -hydroxyvinorelbine and vinorelbin e 6 ' -oxide. All these compounds, including vinblastine (used as internal standard) were deproteinised from blood, plasma and faeces (only diluted in urine), analysed on a cyano column and detected on a Micromass Quattro II system in the positive ion mode after ionisation, using an electrospray ion source. Under tandem mass spectrometry conditions, the specific product io ns led one to accurately quantify vinorelbine and its metabolites in all bi ological fluids. In whole blood, linearity was assessed up to 200 ng/ml for vinorelbine and up to 50 ng/ml for the metabolites. The limit of quantitat ion was validated at 250 pg/ml for both vinorelbine and 4-O-deacetylvinorel bine. In the other biological media, the linearity was assessed within a sa me range and the limit of quantitation was adjusted according to the expect ed concentrations of each compound. This method was initially developed in order to identify the metabolite structures and to elucidate the metabolic pathway of vinorelbine. Thanks to its high sensitivity, this method has ena bled the quantitation of vinorelbine and all its metabolites in whole blood over 168 h (i.e., 4-5 elimination half lives) whilst the previous liquid c hromatographic methods allowed their measurement for a maximum of 48-72 h. Therefore, using this method has improved the reliability of the pharmacoki netic data analysis of vinorelbine. (C) 2001 Elsevier Science B.V. All righ ts reserved.