Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and Validation of Liquid Chromatography-Mass Spectrometry Method for Determination of Febuxostat in Rat Plasma and its Application

A selective liquid chromatography-mass spectrometry (LC–MS) method for determination of febuxostat in rat plasma was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation, and chromatography involved Agilent SB-C18 column (2.1 x150 mm, 5 μm) using 0.1% formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 317 for febuxostat and m/z 326 for midazolam (internal standard, IS). The assay was linear over the range of 10-2000 ng/mL for febuxostat, with a lower limit of quantitation (LLOQ) of 10 ng/mL for febuxostat. Intra- and inter-day RSDs were less than 15% and the accuracies were in the range of 93.8-111.9% for febuxostat. This developed method was successfully applied to determinate of febuxostat in rat plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Irreversible dual inhibitory mode: the novel Btk inhibitor PLS-123 demonstrates promising anti-tumor activity in human B-cell lymphoma.

The B-cell receptor (BCR) signaling pathway has gained significant attention as a therapeutic target in B-cell malignancies. Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lymphoma treatment. Here we present a novel covalent irreversible Btk inhibitor PLS-123 with more potent anti-proliferative activity compared with ibrutinib in multiple cellular and in vivo models through effective apoptosis induction and dual-action inhibitory mode of Btk activation. The phosphorylation of BCR downstream activating AKT/mTOR and MAPK signal pathways was also more significantly reduced after treatment with PLS-123 than ibrutinib. Gene expression profile analysis further suggested that the different selectivity profile of PLS-123 led to significant downregulation of oncogenic gene PTPN11 expression, which might also offer new opportunities beyond what ibrutinib has achieved. In addition, PLS-123 dose-dependently attenuated BCR- and chemokine-mediated lymphoma cell adhesion and migration. Taken together, Btk inhibitor PLS-123 suggested a new direction to pharmacologically modulate Btk function and develop novel therapeutic drug for B-cell lymphoma treatment

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Measuring charge distribution of molecular cations by atomic Coulomb probe microscope

Imaging the charge distributions and structures of molecules and clusters will promote the understanding of the dynamics of the quantum system. Here, we report a method by using an Ar atom as a tip to probe the charge distributions of benzene (Bz) cations in gas phase. Remarkably, the measured charge distributions of Bz cation (QH =0.204,QC=-0.037)and dication (QH =0.248,QC=0.0853)agree well with the calculated Mulliken distributions,and the structures of Bz dimer is reconstructed by using the measured charge distributions. The structures of two Bz dimer isomers (T-shaped and PD isomers) can be resolved from the measured inter-molecular potential V(R) between two Bz ions, and the structures of Bz dimer agree well with the theoretical predictions.Comment: 7 pages, 3 Figure