结合目标数据依赖性MSn方法筛选结构确证碎片信息

前言:

There is an increasing desire to reduce development time and cost devoted to ill-fated lead candidates and therefore a

growing need for complete characterization of each compound earlier in the discovery process. Discovery DMPK experiments are becoming routine resulting in a need for more rapid and automated methods of verification that a putative metabolite is related to the parent drug. Here we present a simplified Precursor Identifying Fragment (PIF) technique which readily lends itself to routine automation and that offers the advantage of metabolite identification with no a priori knowledge of the active pharmaceutical ingredient (API) or any biotransformation products.

结论:

We have defined a Precursor Identifying Fragment (PIF) for Maropitant and used it to tag its metabolites from the precursor ion fingerprint information.

Traditional Precursor ion scanning techniques, although highly selective, are typically less sensitive as they require higher duty cycle in this mode of operation.

In contrast, the ion trap based PIF method we present is both rapid and sensitive due to fundamental duty cycle advantages. In addition, no a priori knowledge of the API or its metabolites is needed, making it amenable to routine automation with significant ease-of-use implications.