LXQ线性离子阱质谱进行代谢物确证和表征的高通量分析方法

前言：

Glyburide is a potent sulfonylurea drug and has been used widely in the treatment of non-insulin-dependent diabetes mellitus for more than 25 years.1-2 The metabolite analysis of glyburide has been carried out using a number

of LC-MS/MS approaches, and hydroxylation has been found to be the major metabolic pathway in most cases.3-6 In addition, other metabolites have also been identified. A previous report using a quadrupole/trap hybrid mass spectrometer claimed to be able to identify 14 metabolites of glyburide incubated with human liver microsomes. Multiple separate LC-MS/MS runs of 45 minutes each were required, which is not an ideal approach for high throughput metabolic profiling, particularly if sample and time are limited. In this report, a rapid LC-MS/MS method was developed for analyzing glyburide and its metabolites in a single run of approximately three minutes using the LXQ.

The rapid LC-MS/MS method made use of Data- Dependent™ acquisitions to study known metabolites and to uncover unexpected metabolites. In addition, data analysis was facilitated by MetWorks and Mass Frontier software that enhanced the screening and characterization of metabolites in complex matrices.

仪器：

LXQ linear ion trap mass spectrometer

结论：

A high throughput LC/MS/MS approach has been developed for metabolic profiling using the LXQ linear ion trap mass spectrometer. The identification and characterization of glyburide along with 19 metabolites was accomplished in a single LC run of approximately three minutes using the fast cycle time, high sensitivity, and excellent spectral quality of this instrument. Compared to previous literature reports, this approach provided a more comprehensive identification of metabolites and eliminated false positives. The use of MetWorks and Mass Frontier software enabled rapid and confident analysis of complicated metabolic profiling data.