Heudi, Olivier, Lanshoeft, Christian, Leuthold, Luc Alexis, Elbast, Walid, Schueller, Fabienne, Picard, Franck and Kretz, Olivier (2014) 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. Analytical and Bioanalytical Chemistry.

Abstract

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 411.4367.4 and m/z 411.4307.4) 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.

Item Type:	Article
Keywords:	LDTD; APCI, LC-MS/MS, SALLE, solid phase extraction, bioanalysis, BKM120, validation and pharmacokinetic.
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21044