采用数据依赖性全扫描和CNL扫描模式进行代谢物鉴定

前言：

This report demonstrates the role of the Thermo Scientific TSQ Quantum Discovery in carrying out in vitro studies of compound metabolic stability and identification of Phase I and II metabolites. For the determination of compound metabolic stability, samples were quantified using SIM and from the metabolic turnover an in vitro half-life was calculated. Full-scan MS/MS Data Dependent scans were carried out for the identification of Phase I metabolites. For phase II metabolites, Constant Neutral Loss (CNL) scans followed by Data Dependent triggered MS/MS analysis were carried out for identification and structural elucidation.

仪器：

TSQ Quantum Discovery mass spectrometer

结论：

The utility of the TSQ Quantum Discovery in early drug discovery for the measurement of a compound’s metabolic stability with rat hepatocytes and for the identification of its phase I and II metabolites has been illustrated. The measurement of the in vitro metabolic turn-over in terms of an in vitro half-life was performed using selective ion monitoring.

The identification of phase I metabolites was facilitated by applying Data Dependent full-scan MS/MS. Phase II metabolites were identified using Constant Neutral Loss scanning especially for glucuronides and glutathione conjugates. A significantly better signal-to-noise ratio in CNL as compared to full-scan could be demonstrated. However, using information of the Data Dependent full-scan MS/MS also for phase II metabolite identification in addition to the CNL scanning can give even more structural information on the metabolite and provides an additional confirmation of the proposed metabolite formation.