Method development and validation for the estimation of gedatolisib in mouse plasma by tandem mass spectrometry and its application to pharmacokinetics studies.

A simple and a sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of gedatolisib in mouse plasma. The extraction technique involved a simple precipitation method to extract gedatolisib and idelalisib (internal standard) from mouse plasma. A clean chromatographic separation of gedatolisib and the internal standard was achieved on an Atlantis dC column using an isocratic mobile phase (10 mm ammonium formate and acetonitrile; 30:70% v/v, both supplemented with 0.

Validated liquid chromatography with tandem mass spectrometry method for determination of paxalisib in mouse plasma: An application to pharmacokinetic study in mice.

A sensitive and rapid LC-MS/MS method has been developed and validated for the quantification of paxalisib in mouse plasma. A liquid-liquid extraction method was used for the extraction of paxalisib and filgotinib (internal standard, IS) from mouse plasma. A clean chromatographic separation of paxalisib and the IS was achieved on an Atlantis dC column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile, 30:70%, v/v) delivered at a flow rate of 0.

Validated HPLC-UV method for quantification of paxalisib, a pan PI3K and mTOR inhibitor in mouse plasma: Application to a pharmacokinetic study in mice.

Paxalisib is a pan-PI3K and mTOR inhibitor, currently entering into Phase II clinical trials as a potential drug to treat glioblastoma patients. We report the development and validation of a high-performance liquid chromatography (HPLC) method for the quantitation of paxalisib in mouse plasma as per the US Food and Drug Administration regulatory guidelines. From the mouse plasma, paxalisib and the internal standard (IS; filgotinib) were extracted using ethyl acetate as an extraction solvent.

Validated LC-MS/MS method for the determination of copanlisib in mouse dried blood spots.

Copanlisib is a dual PI3K-δ inhibitor, used in follicular lymphoma treatment. In this research, we report a validated LC-MS/MS method for quantifying copanlisib from a mouse dried blood spot (DBS). We validated the method in line with the guidelines of the US Food and Drug Administration.

Modulating inhibitory response control through potentiation of GluN2D subunit-containing NMDA receptors.

NMDA receptors containing GluN2D subunits are expressed in the subthalamic nucleus and external globus pallidus, key nuclei of the indirect and hyperdirect pathways of the basal ganglia. This circuitry integrates cortical input with dopaminergic signaling to select advantageous behaviors among available choices. In the experiments described here, we characterized the effects of PTC-174, a novel positive allosteric modulator (PAM) of GluN2D subunit-containing NMDA receptors, on response control regulated by this circuitry.

Prediction of Human Pharmacokinetics of Ulixertinib, a Novel ERK1/2 Inhibitor from Mice, Rats, and Dogs Pharmacokinetics.

Background And Objectives: Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. The primary objectives of the study were to evaluate the pharmacokinetics of ulixertinib in mice, rats, and dogs followed by prediction of human pharmacokinetic profile by allometric equations with/without correction factors.

Methods: Oral and intravenous pharmacokinetic profiles of ulixertinib were generated in mice, rats, and dogs.

Preclinical assessment of Orteronel(®), a CYP17A1 enzyme inhibitor in rats.

Orteronel (TAK-700) is a novel and selective inhibitor of CYP17A1, which is expressed in testicular, adrenal and prostate tumor tissues. Orteronel is currently in Phase-III clinical development for metastatic castration-resistant prostate patients. The objective of the study is to assess the permeability, metabolic stability (in various preclinical and human liver microsomes), identify the major CYPs involved in the metabolism of Orteronel.

Determination of theophylline in rabbit plasma by triple quadrupole LC/MS.

Aim And Background: A simple, sensitive and rapid method was developed for quantitation of theophylline in rabbit plasma utilizing Triple Quadrupole LC/MS.

Materials And Methods: An aliquot of 0.1 mL of plasma sample was extracted with ethyl acetate using Heidolph Vortex.