Aim: Tregopil, a novel PEGylated human insulin is in clinical development for oral delivery in diabetes treatment. The aim of the study was to develop and validate a sensitive and specific ELISA method for quantitating Tregopil in diabetes subjects on basal Glargine, since most commercially available insulin kits either do not detect Tregopil or show […]
Aim: Incurred sample reanalysis (ISR) contributes to the reliability of pharmacokinetic studies. Despite regulatory guidelines having adopted ISR methodology, graphical presentation of data has been overlooked. Materials & methods: Different graphs were tested for datasets including limited, standard and large numbers of ISR pairs. The datasets covered both passed and failed cases. Results: We have
Aim: We evaluated three immunoassay-based technologies and their biomarker kits, by determining precision, parallelism and detectability of analytes of interest. Materials & methods: We compared ultrasensitive assays for three biomarkers: interleukins IL-6, IL-13 and IL-17A using kits obtained from Roche (IMPACT platform – proprietary platform), Singulex (Erenna®) and Quanterix (Simoa™). We defined the true LLOD
Aim: Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. Materials & methods: An HPLC-Q-Orbitrap method (based on HPLC–MS/MS) was developed and validated for the simultaneous detection and quantitation of six tyrosine kinase
Aim: Critical illness and medical interventions, such as renal replacement therapy, can cause changes to vancomycin pharmacokinetics and lead to suboptimal dosing. To comprehensively characterize vancomycin pharmacokinetic a method must measure vancomycin in a range of clinical matrices. Results: A LC–MS/MS method was developed using hydrophilic interaction liquid chromatography and microsample volumes, where possible. For
Aim: Bridging immunoassays for detection of antidrug antibodies (ADAs) are typically susceptible to high concentrations of residual drug. Sensitive drug-tolerant assays are, therefore, needed. Materials & methods: An immune complex assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation was established. The assay uses antibodies specific for the Pro329Gly mutation for capture and human
Aim: 5α-androst-3β,5,6β-triol is a novel ischemic stroke drug under clinical development. The objective of this study was to develop and validate a simple ultraperformance liquid chromatography tandem mass spectrometry method for 5α-androst-3β,5,6β-triol in human plasma and its application in clinical pharmacokinetic study. Methodology & results: After being pretreated using an automatized solid-phase extraction procedure, plasma
Aim: Toxicokinetic and pharmacokinetic studies of therapeutic oligonucleotides require validated bioanalytical methods for sensitive and specific quantification of oligonucleotide drug candidates in biological samples. Results: A peptide nucleic acid (PNA) hybridization-based HPLC-fluorescence assay was developed and validated for quantification of Arrowhead Pharmaceuticals’ proprietary siRNA in rat plasma samples via hybridization and anion-exchange-HPLC (AEX-HPLC) with fluorescence
Aim: Bridging immunoassays for detection of antidrug antibodies (ADAs) are typically susceptible to high concentrations of residual drug. Sensitive drug-tolerant assays are, therefore, needed. Materials & methods: An immune complex assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation was established. The assay uses antibodies specific for the Pro329Gly mutation for capture and human
Aim: AVI-7100 (Radavirsen) is a 20-mer phosphorodiamidate morpholino oligomer (PMOplus®) for the treatment of influenza. Results/methodology: An automated solid-phase extraction method was used to extract plasma samples (200 μl). The extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry under the positive ionization mode. This method was fully validated over the calibration curve