Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7626185 | Journal of Pharmaceutical and Biomedical Analysis | 2018 | 17 Pages |
Abstract
Lurbinectedin is a novel highly selective inhibitor of RNA polymerase II triggering caspase-dependent apoptosis of cancerous cells. This article describes the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify lurbinectedin in human plasma and urine. Plasma samples were pre-treated with 1â¯M aqueous ammonia after which they were brought onto supported liquid extraction (SLE) columns. Lurbinectedin was eluted from the columns using tert-butyl methyl ether (TBME). Urine was first diluted in plasma and lurbinectedin was extracted from this matrix by liquid-liquid extraction using TBME. Samples were measured by LC-MS/MS in the positive electron ion spray mode. The method was linear over 0.1-100â¯ng/mL and 1-1000â¯ng/mL in plasma and urine, respectively, with accuracies and precisions within ±15% (20% for LLOQ) and below 15% (20% for LLOQ), respectively. The method was developed to support a mass balance study in which patients received a dose of 5â¯mg lurbinectedin.
Keywords
tBMEMRMGCPEMARPMGLPLurbinectedinLLEULOQLiquid Chromatography – Tandem Mass SpectrometryFDALLOQDMSOHPLC–MS/MSLC–MS/MSEuropean Medicine AgencyUrineinternal standardCalibration standardSupported liquid extractionliquid liquid extractionBioanalysistert-butyl methyl etherGood Laboratory Practiceupper limit of quantificationlower limit of quantificationDimethylsulfoxideFood and Drug AdministrationCoefficient of Variationmatrix factorgood clinical practiceSLEmultiple reaction monitoringPlasmarotations per minutequality control
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
L. van Andel, H. Rosing, R. Lubomirov, P. Avilés, S. Fudio, M.M. Tibben, L. Nan-Offeringa, J.H.M. Schellens, J.H. Beijnen,