With decommissioning of internal regulated bioanalytical (BA) and toxicokinetic (TK) capabilities, Novartis has relied on external service providers (ESPs) for all nonclinical LC–MS BA and majority of the associated TK work since 2017. This paper outlines an integrated outsourcing practice of the Novartis nonclinical LC–MS BA/TK group, which covers the roles and responsibilities of Novartis […]
Aim: Quantification of stereoisomers in biological matrices is of pivotal importance for drug development. Supercritical fluid chromatography paired with chiral stationary phases is the gold standard for resolution of enantiomers. However, this technique often proves inadequate for resolution of polar stereoisomers. Materials & methods: A combination of achiral chemical derivatization with supercritical fluid chromatography using
Aim: Green, accurate and rapid methods, namely LC–MS/MS and thin layer chromatography-densitometric methods, were developed for determination of amlodipine besylate and celecoxib in presence of its process-related impurities, 4-methylacetophenone in pure and formulated tablets. Results: LC–MS/MS was achieved on ZORBAX Eclipse Plus C18 column using methanol:aqueous solution of 5 mM formic acid (95:5 v/v). High
Aim: Glycopyrrolate (GLY) has been widely used to treat chronic obstructive pulmonary disease (COPD). Recent technical advancement significantly improves the drug delivery efficiency. In a clinical dose-range determination study via electronic nebulizer, the starting dose was as low as 3-μg, thus, a bioanalytical method capable of measuring down to sub-pg/ml or fg/ml level was required
The foundation of pharmacokinetics and antidrug antibodies assay robustness relies on the use of high-quality reagents. Over the past decade, there has been increasing interest within the pharmaceutical industry, as well as regulators, on defining best practices and scientific approaches for generation, characterization and handling of critical reagents. In this review, we will discuss current
Flow cytometer is a powerful cellular analysis tool consists of three main components; fluidics, optics and electronics. Flow cytometry methods have been used in all stages of drug development as like ligand binding assays (LBA). Both LBA and flow cytometry methods require specific interaction between the critical reagents and the analytes. Antibodies and their conjugates,
Aim: Critical reagents have significant impact on ligand-binding assay performance. The critical reagents selected during method development should be well-evaluated, as the quality of these reagents will dictate performance of the assay over time. Critical reagents in ligand-binding assays are almost always produced using a biological system, so batch yield, purity and performance tend to
We have evaluated the utility of epitope binning on biolayer interferometry (BLI) as a strategy to funnel the selection of candidate pairs suitable for pharmacokinetic assay development. Totally, 8 anti-Idiotypic monoclonal antibodies in 64 possible combinations were tested by BLI, ELISA and Gyrolab®. Two epitope binning approaches were utilized, in-tandem and classic sandwich. Both formats
The increasing number of biopharmaceuticals, gene and cell therapies in development has seen a growing use of flow cytometry to measure biomarkers, generate pharmacokinetic data, assess immunogenicity and investigate target engagement. The importance of these data types and their inclusion in regulatory submissions mean that flow cytometry analyses are now expected to demonstrate robust performance
Background: A valine carbamate prodrug (7-P) was designed to enhance the low bioavailability of daidzein due to its low water solubility and membrane permeability. Here, we developed a high-throughput HPLC–MS/MS method to measure daidzein and its 7-O-glucuronide after oral administration of daidzein or 7-P. Materials & methods: A HPLC–MS/MS method was validated and successfully applied