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Laser diode thermal desorption atmospheric pressure chemical ionization tandem mass spectrometry applied for the ultra-fast quantitative analysis of BKM120 in human plasma

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Abstract

A sensitive and ultra-fast method utilizing the laser diode thermal desorption ion source using atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for the quantitative analysis of BKM120, an investigational anticancer drug in human plasma. Samples originating from protein precipitation (PP) followed by salting-out assisted liquid-liquid extraction (SALLE) were spotted onto the LazWell™ plate prior to their thermal desorption and detection by tandem mass spectrometry in positive mode. The validated method described in this paper presents a high absolute extraction recovery (>90 %) for BKM120 and its internal standard (ISTD) [D8]BKM120, with precision and accuracy meeting the acceptance criteria. Standard curves were linear over the range of 5.00 to 2000 ng mL−1 with a coefficient of determination (R 2) >0.995. The method specificity was demonstrated in six different batches of human plasma. Intra- and inter-run precision as well as accuracy within ±20 % at the lower limit of quantification (LLOQ) and ±15 % (other levels) were achieved during a three-run validation for quality control (QC) samples. The post-preparative stability on the LazWell™ plate at room temperature was 72 h and a 200-fold dilution of spiked samples was demonstrated. The method was applied successfully to three clinical studies (n = 847) and cross-checked with the validated LC-ESI-MS/MS reference method. The sample analysis run time was 10 s as compared to 4.5 min for the current validated LC-ESI-MS/MS method. The resultant data were in agreement with the results obtained using the validated reference LC-ESI-MS/MS assay and the same pharmacokinetic (PK) parameters were calculated for both analytical assays. This work demonstrates that LDTD-APCI-MS/MS is a reliable method for the ultra-fast quantitative analysis of BKM120 which can be used to speed-up and support its bioanalysis in the frame of the clinical trials.

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Acknowledgments

This work was conducted in fulfillment for the degree of M. Sc. in Life Sciences (University of Applied Sciences Northwestern Switzerland, School of Life Sciences). As the LC-ESI-MS/MS assay was performed previously, we would like to thank Fabienne Schueller, Lucie Barotte and Marc Raccuglia for technical assistance. Furthermore, we would like to thank Eleni Dimitriadou (M. Sc.) for reviewing the manuscript from a language point of view.

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Authors and Affiliations

  1. Novartis Pharma AG, DMPK/Bioanalytics, Forum 1 Novartis Campus, 4056, Basel, Switzerland

    Christian Lanshoeft, Olivier Heudi, Luc Alexis Leuthold, Walid Elbast, Franck Picard & Olivier Kretz

  2. School of Life Sciences, Institute for Chemistry and Bioanalytics, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, 4132, Muttenz, Switzerland

    Götz Schlotterbeck

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  1. Christian Lanshoeft
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  2. Olivier Heudi
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Correspondence to Olivier Heudi.

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Lanshoeft, C., Heudi, O., Leuthold, L.A. et al. Laser diode thermal desorption atmospheric pressure chemical ionization tandem mass spectrometry applied for the ultra-fast quantitative analysis of BKM120 in human plasma. Anal Bioanal Chem 406, 5413–5423 (2014). https://doi.org/10.1007/s00216-014-7966-6

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  • DOI: https://doi.org/10.1007/s00216-014-7966-6

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