Tandem Labs

DMDiscovery^SM

For drug molecule metabolite screening, surveying, and identification, Tandem Labs uses its innovative drug metabolism informatics technology, DMDiscovery^SM, to efficiently and effectively process and analyze high resolution, accurate mass data derived from two complimentary mass spectrometry platforms: MALDI/TOF/TOF and LC/QTOF. As always, Tandem Labs is driven to provide clients with quality data that satisfies their specific experimental objectives in the shortest possible time.

Tandem Labs offers the following service categories for metabolite screening and identification:

• DMDiscovery^SM Level 1: Metabolite Screening

  Applicable to the early stage screening of compounds where the objective is to improve the PK/PD characteristics of compounds within a series that are built upon a common scaffold, e.g., identification and design mediation of compound-metabolic 'hot spots'.

• DMDiscovery^SM Level 2: Metabolite Surveying

  Applicable to the later stages of discovery where the objective may be the optimization of a lead candidate compound(s) PK/PD, e.g., determination of specific sites of hydroxylation and oxidation, among others, and their relative rates.

• DMDiscovery^SM Level 3: Metabolite Identification and Pathways

  Applicable to compound development (non-clinical or clinical) or candidate nomination where the objective is to comprehensively identify the full range of drug compound metabolites to assist in the design of their respective development programs, e.g., the identification of species-specific metabolites and metabolites for safety testing (MIST), among others.

Summary of Metabolite Screening and Identification Services, Strategies, and Outcomes

Technology	Process
	Service Category	Data Collection	Raw Data & Data Processing	Mass Accuracy	Outcomes
LC/MS/MS	DMDiscoverySM I & II (Metabolite Screening and Surveying	MRM Scan	Instrument Vendor Software	Unit Mass	• Common metabolic alterations • May not identify modification sites1 • Cannot identify modification types (e.g., -NH2 vs. -O)
		Precursor Ion Scan
		Precursor Ion Scan
		Neutral Loss Scan
LC-QTOF	DMDiscoverySM II & III (Metabolite Surveying, ID, and Pathways)	LC/MS	Instrument Vendor Software & DMDiscoverySM	Accurate Mass	• Common metabolic alterations • May not identify modifications sites1 • Identify modifications types (e.g., -NH2 vs. -O)
		LC/MS/MS
MALDI-TOF	DMDiscoverySM III (Metabolite ID and Pathways)	MS	Instrument Vendor Software & DMDiscoverySM	Accurate Mass	• Common metabolic alterations • May not identify modifications sites1 • Identify modifications types3 (e.g., -NH2 vs. -O)
		MS/MS
NOTES 1 - Site of modifications contingent upon LC separation. 2 - High accurate mass MS/MS may enable determination of site modifications 3 - High energy accurate mass MS/MS enables determination of site modification. DMDiscoverySM is a proprietary informatics system enabling accelerated data processing and mining.

Graphic Deptiction of Accelerated Metabolite Identification Service Category as it Relates to the Drub Discovery and Development Process