Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7615236 | Journal of Chromatography B | 2018 | 5 Pages |
Abstract
A bio-analytical assay for the first third generation ALK inhibitor lorlatinib in mouse plasma was developed and validated. Ten-μl plasma samples were prepared by adding rucaparib as the internal standard and precipitation of the plasma proteins. For LC-MS/MS analysis, compounds were eluted at 0.5â¯mL/min and separated on a 3-μm particle-size, polar embedded octadecyl silica column by gradient elution using 0.1% of formic acid (in water) and methanol. Compounds were monitored with positive electrospray ionization using a triple quadrupole mass spectrometer in selected reaction monitoring mode. The assay was fully validated in the 2-2000â¯ng/mL calibration range. Withinâday (8.0-11.6%) and betweenâday (10.0-15.0%) precisions and accuracies (99.0-113.3%) were within acceptable range. Plasma samples were deemed stable for 6â¯h at ambient temperature, during three freeze-thaw cycles and for 2â¯months at â30â¯Â°C. Finally, the new assay was applied successfully to pilot pharmacokinetic studies in male and female wild-type mice.
Keywords
LLOQEchinoderm microtubule-associated protein-like 4EML4FDALorlatinibNPMROS1EMAESISRMLC-MS/MSALKEuropean Medicines agencyinternal standardlower limit of quantificationFood and Drug AdministrationNon-small lung cancerNSCLCLiquid chromatography-tandem mass spectrometryAnaplastic lymphoma kinaseALK inhibitorselected reaction monitoringnucleophosminMouse plasmaquality controlElectro spray ionization
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Claudia Spatari, Wenlong Li, Alfred H. Schinkel, Gaetano Ragno, Jan H.M. Schellens, Jos H. Beijnen, Rolf W. Sparidans,