结合使用LTQ Orbitrap XL多重质量亏损过滤和高能量碰撞解离实现快速、灵敏、准确代谢物鉴定

前言：

Purpose: To evaluate the use of Multiple Mass Defect ilters (MMDFs)™ with LTQ Orbitrap XL data for etabolite identification; to investigate the use of Higher nergy Collisional Dissociation (HCD) for structural lucidation in metabolite identification experiments.

Methods: Rat hepatocyte incubation samples of Irinotecan ere analyzed using an LTQ Orbitrap XL with HCD ollision cell. Both Collision Induced Dissociation (CID) S/MS and HCD MS/MS were acquired for the potential etabolites. MMDFs were then used to process the cquired raw file.

Results: MMDFs were able to filter out the vast majority of he background ions in the full scan spectra while preserving hose related to the parent drug. Compared with the esults gathered from using only a single Mass Defect Filter MDF), results from MMDFs are more distinct and specific, llowing users to do faster, more sensitive and more accurate nalyses. HCD provides complementary fragmentation athways, in addition to the CID available in the ion trap, nd produces low mass diagnostic ions in MS/MS spectra hat are useful for metabolite structural elucidation.

仪器：

LTQ Orbitrap XL mass spectrometer

结论：

With the help of MMDF and the combination of HCD and ID MS/MS, 13 Irinotecan metabolites whose peak areas ere less than 1% of that of the parent were identified on n LTQ Orbitrap XL coupled to an Accela High Speed LC.

This report demonstrates that MMDF is more effective han a single MDF to uncover phase I and II metabolites pecifically and concurrently. It also allows the detection of etabolites from hydrolysis or N-dealkylation, even when he products from such processes have mass defects that re significantly different from the parent. MMDF allows sers to use low threshold values during data processing o that metabolites at very low levels can be easily identified. he resulting chromatogram from MMDF is accurate nd specific because it is based on exact mass and mass eficiencies, which are highly specific to the parent drug ompound. It provides speed, sensitivity and accuracy to acilitate the identification of drug metabolites in drug iscovery and development.

HCD provides an alternative fragmentation method n the LTQ Orbitrap XL in addition to the CID in the inear ion trap. HCD spectra display characteristics similar o those from a quadrupole collision cell: rich in product ons, has no low mass cut off, and typically a portion of he parent ions still remains. The fragment ions in HCD pectra have high mass accuracy and resolution. These haracteristics of HCD spectra complement the power f ion trap MSn and allow easy spectrum interpretation nd high confidence in structural elucidation.