Li, Wenkui, Lin, Hui, Flarakos, Jimmy and Tse, Francis (2013) Practical Approaches to Incurred Sample LC-MS/MS Reanalysis: Confirming Unexpected Results. Analytical Chemistry.

Abstract

Incurred sample reanalysis (ISR) is an important step in assuring the quality of an LC-MS/MS bioanalytical assay and the integrity of bioanalysis conduct. A conventional ISR involves analysis of at least 20 samples taken from an in vivo study a second time using the method that was described in pre-study validation and employed in generating the initial study sample results. However, this practice is sometimes inadequate to confirm bioanalytical results that are unexpected. The present report discuss several additional exploratory activities that were performed to confirm the unexpected plasma concentration-time results of NVP-1, an investigational drug candidate, observed in the plasma samples collected from patients in a phase II trial. These approaches include (1) LC-MS/MS reanalysis of the study samples after multiple freeze/thaw cycles followed by a short term bench top storage, (2) evaluation of additional MS/MS transitions in LC-MS/MS, (3) employment of different sample preparation procedure in LC-MS/MS and (4) study sample dilution using plasma samples from healthy volunteers. These procedures are practical and can be readily implemented to provide confirmatory LC-MS/MS bioanalysis of other small molecules.

Item Type:	Article
Keywords:	Incurred sample reanalysis; Bioanalysis; Incurred sample accuracy; Multichannel LC-MS/MS; Incurred sample short term stability.
Date Deposited:	27 Apr 2016 23:45
Last Modified:	27 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/8796