Non-regulated LC-MS/MS bioanalysis in support of early drug development: a Novartis perspective.

Abstract

Scientifically qualified LC-MS/MS methods are essential for the determination of small molecule drug candidates and/or their metabolite(s) in support of various non-regulated safety assessment and in vivo absorption, distribution, metabolism and excretion studies in preclinical development. This articleoutlines an effective method development workflow to fit for this purpose. The workflow features a 'universal' protein precipitation solvent for efficient sample extraction, a mobile phase additive for managing chromatographic resolution and addressing carryoverand an internal standard cocktail to select the best analogue internal standard to track the analyte of interest in LC-MS/MS. In addition, good practices arerecommended to prevent bioanalytical pitfalls due to instability, non-specific bindingand dosing vehicle-induced matrix effect. Proper handling of non-liquid matrix isalso discussed.