Determination of the antidepressant levoprotiline and its N-desmethyl metabolite in biological fluids by gas chromatography/mass spectrometry.

A specific and sensitive gas chromatographic/mass spectrometric method was developed and validated for the determination of the antidepressant levoprotiline in blood, plasma and urine and the simultaneous determination of levoprotiline and its desmethyl metabolite in urine. Deuterium-labelled analogues were used as internal standards. The compounds were isolated from the biological fluids by liquid-liquid extraction under basic conditions. Following derivatization with perfluoropropionic anhydride, the samples were analysed by capillary column gas chromatography/electron impact mass spectrometry with selected ion monitoring. The analysis of spiked samples demonstrated the high accuracy and precision of the method. Blood concentrations of levoprotiline down to 0.7 nmol l-1 (1 ml used for analysis) could be quantified with a coefficient of variation of 10% or less. The method is suitable for use in pharmacokinetic and bioavailability studies of levoprotiline in humans

Laser Diode Thermal Desorption-positive mode Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry applied for the ultra-fast quantitative analysis of BKM120 in human plasma: method validation and its application to clinical studies

A sensitive and ultra-fast method utilizing the LDTD-APCI ion source coupled to tandem mass spectrometry was developed and validated for the quantitative analysis of BKM120 in human plasma. Samples originating from protein precipitation (PP) followed by salting-out assisted liquid-liquid extraction (SALLE) were spotted on the LazWell™ plate prior their thermal desorption and analysis by tandem mass spectrometry. Two MRM transitions (m/z 411.4367.4 and m/z 411.4307.4) were used to quantify BKM120. The present method was validated in terms of selectivity, linearity, accuracy, precision, stability, extraction recovery and matrix effect. The linearity of the method was found to be within the concentration range of 5.00 and 2000 ng mL-1. The sample analysis run time was 10 seconds as compared to 4.5 min for the current validated LC-ESI-MS/MS method. The LDTD-APCI-MS/MS method was successfully applied for the analysis of BKM120 in clinical samples obtained from 3 clinical studies. The resultant data was consistent with the results obtained with the validated LC-ESI-MS/MS assay. This work demonstrates that LDTD-APCI-MS/MS is a reliable method for the ultra-fast quantitative analysis of BKM120 and can be used to support its bioanalysis in the frame of the clinical trials

Glycosinolates et angiogenèse tumorale

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