APPLICATION OF MULTIVARIATE ANALYSIS for DETERMINING METABOLIC PROFILES of DRUGS: A CASE STUDY USING NEFAZODONE

摘要

A simple and rapid protocol of two injections per group of samples is needed to: 1) generate the MS/retention-time data pair for PCA analysis. 2) generate the EMS/EPI data for structural identification. Multiple injections per group revealed good reproducibility between control and dosed sample sets (see MarkerView chromatograms). Compared to conventional methods of data generation and analysis (numerous injections for precursor &/or product ion scans), little manual intervention is needed (post acquisition) to identify metabolites from the PCA and corresponding MS/MS spectra. Half of the metabolites identified with the PCA method resulted from cleavage around nefazodone's piperidine moiety. Unlike predictive metabolite software (commercially available) that is not readily able to predict metabolites resulting from enzymatic cleavage, the PCA approach easily identifies these metabolites with no prior knowledge of the structure or metabolic processes.