Metabo Lynx Automating Drug Metabolism Studies What is

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Metabo. Lynx Automating Drug Metabolism Studies

Metabo. Lynx Automating Drug Metabolism Studies

What is Metabo. Lynx? • Metabo. Lynx is the application manager for automated processing

What is Metabo. Lynx? • Metabo. Lynx is the application manager for automated processing and reporting of metabolism data • It is an extension of Mass. Lynx designed specifically for this application • Metabo. Lynx accelerates the processing and reporting of drug metabolism data • It can help to carry out data manipulation in hours (minutes) where it would previously have taken days (hours)

What is required? • Many metabolites can be predicted • Processing is time-consuming and

What is required? • Many metabolites can be predicted • Processing is time-consuming and repetitive • NEED AUTOMATED PROCESSING • Not all metabolites can be predicted • Need to search data for unknowns • They may be hidden by abundant endogenous peaks • Data processing is extremely labour-intensive • NEED AUTOMATED PROCESSING • May need to acquire MS/MS data • Set-up, processing and reporting is timeconsuming

Metabo. Lynx Flow Path LC/MS Report LC/MS results Acquire control & metabolized samples Metabo.

Metabo. Lynx Flow Path LC/MS Report LC/MS results Acquire control & metabolized samples Metabo. Lynx Search expected & unexpected Create MS/MS method Auto-start MS/MS Process MS/MS data Append to report Control comparison

Metabo. Lynx Set-up • • • Flexible parameters - discovery or development Batch or

Metabo. Lynx Set-up • • • Flexible parameters - discovery or development Batch or single sample analysis Expected metabolites menu Unexpected metabolites Control sample Search data using MS, PDA or analog • radioactivity detection, fluorescence, etc. • Exact mass measurement and elemental composition • Isotope cluster search • chlorine, bromine, isotopic labeling • Automated MS/MS set-up

Metabo. Lynx Set-up - Peak Detection

Metabo. Lynx Set-up - Peak Detection

Metabo. Lynx Set-up - Expected Metabolites

Metabo. Lynx Set-up - Expected Metabolites

Unexpected Metabolites • • • Small peaks in complex matrices Requires intensive data mining

Unexpected Metabolites • • • Small peaks in complex matrices Requires intensive data mining Greatest time-saving through automation Using chromatogram peak detection User defined step size and thresholds

Control Comparison • • Direct subtraction not feasible Acquire control and experimental sample Process

Control Comparison • • Direct subtraction not feasible Acquire control and experimental sample Process control and experimental sample Identify peaks by mass, RT and response Specify windows for RT and response Filter out matching peaks Utility depends on control sample

Metabo. Lynx Set-up - Isotope Clusters

Metabo. Lynx Set-up - Isotope Clusters

Isotope Cluster Plot (Br)

Isotope Cluster Plot (Br)

Data Visualization - Metabo. Lynx Browser

Data Visualization - Metabo. Lynx Browser

Automated LC-MS/MS • Creates and starts LC-MS/MS acquisition • • builds MS/MS method based

Automated LC-MS/MS • Creates and starts LC-MS/MS acquisition • • builds MS/MS method based on browser report creates new sample list creates new file name(s) and sample text automatically starts MS/MS (product ion) acquisition can choose full automation or manual intervention processes MS/MS data adds data to LC-MS report file and browser

Metabo. Lynx Browser - MS/MS

Metabo. Lynx Browser - MS/MS

Instrument Compatibility • ZMD / ZQ (single quad) • LC-MS • Quattro micro /

Instrument Compatibility • ZMD / ZQ (single quad) • LC-MS • Quattro micro / LC / Ultima (triple quad) • LC-MS/MS • processing of precursor and neutral loss data • LCT (oa-TOF) • exact mass LC-MS • Q-TOF micro / II / Ultima • exact mass LC-MS and LC-MS/MS • GCT (GC-TOF)

Metabo. Lynx - Summary • Automation of metabolism studies • Flexibility for metabolite screening

Metabo. Lynx - Summary • Automation of metabolism studies • Flexibility for metabolite screening or low level detection • Speed • sample throughput in discovery • data mining in development • Data visualisation and reporting • Not just metabolism • Impurity studies • Further developments on-going