Aim: A sensitive HPLC–MS/MS approach was established to quantify trelagliptin and explore the pharmacokinetic characteristics in rats for up to 7 days. Meanwhile, the pharmacokinetic differences of trelagliptin were investigated for the first time. Results/methodology: The ion pairs of m/z 358.2→341.2 for trelagliptin and m/z 340.3→116.1 for alogliptin (internal standard) were detected in positive mode. […]
Aim: Collection and quantitative analysis in dry blood using volumetric absorptive microsampling (VAMS™) potentially offers significant advantages over conventional wet whole blood analysis. This manuscript explores their use for pediatric sampling and explores additional considerations for the validation of the bioanalytical method. Results: HPLC–MS/MS methods for the determination of midazolam and its major metabolite 1-OH
Therapeutic protein drugs have significantly improved the management of many severe and chronic diseases. However, their development and optimal clinical application are complicated by the induction of unwanted immune responses. Therapeutic protein-induced antidrug antibodies can alter drug pharmacokinetics and pharmacodynamics leading to impaired efficacy and occasionally serious safety issues. There has been a growing interest
Biological drug products may elicit an antidrug antibody (ADA) response. The current widely used bridging ligand binding assay (LBA) is the gold standard for ADA assessments in drug development, which is a qualitative assay followed by a quasi-quantitative titer analysis but can be prone to interferences from biological matrices, drug targets and circulating drugs. We
Background: Soluble drug target in clinical study samples generated false positive results in anti-drug antibody (ADA) bridging assays due to target-mediated bridging. Results: The combination of two target-blocking reagents and mild basic assay pH resulted in high tolerance to recombinant target protein and reduced levels of positivity in clinical study samples with pharmacokinetic profiles that
Biography Gopi Shankar is a Vice President at Janssen BioTherapeutics, the biotechnology discovery and development unit of Janssen Research & Development, LLC (one of the Pharmaceutical Companies of Johnson & Johnson). His department of approximately 150 scientists is responsible for characterizing biophysical and pharmacological parameters of biologic molecules for discovery and for developing preclinical projects
Aim: Solid-phase microextraction is proposed to measure concentrations of anandamide and 2-arachidonoyl glycerol in live rat brains in response to stress. Materials & methods: Solid-phase microextraction fibers were prepared from steel with 1.5 mm extraction coating. 24 male rats were divided into groups based on brain region, stria terminalis or posterior hypothalamus and loud noise
Aim: This study aimed: to develop and validate an LC–MS/MS method for mycophenolic acid, tacrolimus, sirolimus, everolimus and cyclosporin A in oral fluid (OF), as an essential tool to study the usefulness of OF as an alternative matrix for immunossuppressants’ therapeutic drug monitoring; and to find the best OF collector for these analytes. Materials &
Aim: CX1003 is a novel multitargeted receptor tyrosine kinase inhibitor targeting cancer patients with relapsed or metastatic malignant solid tumors. The study aimed to develop a robust and rapid assay approach to quantify CX1003 in human plasma. Methodology & results: Samples of plasma were purified by SPE where the diluted eluates were then separated by
Aim: Pharmacokinetics after oral microdosing of the anticipated CYP2D6 substrate yohimbine and its metabolite 11-OH-yohimbine is potentially useful for drug–drug interaction trials and profiling of CYP2D6 enzyme activity. Materials & methods: We developed an ultrasensitive ultra performance liquid chromatography coupled to tandem mass spectrometry assay for quantification of yohimbine and its main metabolite 11-OH-yohimbine in