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

• Published in: Analytical and bioanalytical chemistry Vol. 406; no. 22; pp. 5413 - 5423
• Main Authors: Lanshoeft, Christian, Heudi, Olivier, Leuthold, Luc Alexis, Schlotterbeck, Götz, Elbast, Walid, Picard, Franck, Kretz, Olivier
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-09-2014; Springer Berlin Heidelberg; Springer; Springer Nature B.V
• Subjects: Accuracy; Amino acids; Aminopyridines - blood; Analysis; Analytical Chemistry; Antimitotic agents; Antineoplastic agents; Atmosphere; Atmospheric Pressure; Atmospherics; Biochemistry; Blood plasma; Calibration; Characterization and Evaluation of Materials; Chemical properties; Chemistry; Chemistry and Materials Science; Chemistry, Pharmaceutical - methods; Chromatography; Chromatography, Liquid; Clinical trials; Desorption; Electrochemistry; Food Science; Human; Humans; Ionization; Laboratory Medicine; Laser diodes; Lasers; Linear Models; Liquid-liquid extraction; Liquid-Liquid Extraction - methods; Mass spectrometry; Measurement; Monitoring/Environmental Analysis; Morpholines - blood; Pharmacokinetics; Plasma; Plasma - chemistry; Quality Control; Quantitative analysis; Reference Values; Reproducibility of Results; Research Paper; Scientific imaging; Spectrometry, Mass, Electrospray Ionization; Spectroscopy; tandem mass spectrometry; Tandem Mass Spectrometry - methods; Temperature; Time Factors; Water analysis; United States > US; Switzerland; Liquid chromatography tandem mass spectrometry; Validation; Salting-out assisted liquid-liquid extraction; Bioanalysis; Laser diode thermal desorption; Pharmacokinetic
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-014-7966-6

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.