Organisational Learning in Chromatography · Organisational Learning in Chromatography Mike...
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Organisational Learning in Chromatography Mike McBrien, Andrey Vazhentsev, Dima Tzarev, and Susan Ling Advanced Chemistry Development, Inc., (ACD/Labs), Toronto, Ontario, Canada Introduction Chromatography is a popular analytical technique used in organisations across a wide range of chemistry-related endeavours. Chromatographic results collected from different instruments are typically segmented and therefore contribute very little to organisational learning. In order to establish a true chromatographic knowledgebase, it is necessary to store and relate processed data to its chemical context. When established, a chromatographic knowledgebase can form the backbone of systems for chromatographic prediction and method selection, and facilitate interpretation of new samples. Data files Molecule Registries db Laboratory Notebooks ELNs Reports Figure 1: The silos that typically separate chromatographic knowledge in an organisation. Architecture A chromatographic knowledgebase must not only include chromatographic data, but also relate that information to its chemical context. The critical aspects of this context can be subtly different depending on the proposed application, but can be generalized as the interpretation of the data. Chemical context may include sample names, spectral-peak assignments, or structures linked to elution data with methods. ACD/SpecDB and ACD/ChromGenius are knowledgebases that are designed to relate stored chromatographic data, including spectra, components, and chromatographic peaks, to their chemical context, such as structures, elution tRs, and chromatographic methods, respectively. Automation It is rare in modern business to have the luxury of dedicated instruments and systems to automate the routine of chromatographic work and establish even the most critical of efficiency systems. Any workflow designed to accumulate knowledge must be an offshoot of an analysis that is already being done, and require little to no manual effort on the part of the chromatographer. Ideally, the accumulation should be part of an approach to increase the accuracy and efficiency of the primary objective. ACD/AutoChrom’s method development system and ACD/Automation Server’s scripting engine are designed to automatically store the data collected and interpret the analytical information. Component detection and identification results can be generated more efficiently, and transferred to the knowledgebase in the background, with little to no additional effort on the part of the analyst. In both cases, the primary goal of automation is the streamlining of day-to-day operations. Leveraging the Knowledge 1. Chiral Method Selection The Automated Chromatographic Application Databasing System (ACADES) is a method development solution particularly suited to chiral methods. Chiral screening results are automatically reviewed and linked to chemical structures and methods. Reports are automatically generated, and the results (positive and negative) of each screen are passed to the knowledgebase. The screens then form the basis of structure-based method prioritisation, reducing the number of experiments required for new samples. Storage Network File Archive (raw or processed data) SpecDB Automation Server Macro Document Management Figure 2: ACADES applied to chiral method development. Storage of screening results provides the basis for structure-based prioritisation of screens for new samples. 2. Achiral Generic Method Selection Both ACADES and AutoChrom can be applied to create a knowledgebase for the prediction of elution in achiral methods. In this case, explicit prediction of elution (as opposed to selectivity) is possible through the ChromGenius application. Once established, it is possible to enter one or more structures, and generate predicted chromatograms for all generic methods. Sample Creation Structure/Retention Knowledgebase Method Selection System Training Cl O O CH 3 Cl O O CH 3 t R Figure 3: Structures attached to peaks, arranged by method, provide the basis for ChromGenius’ prediction of new chromatograms and subsequent method selection. 3. Sample Interpretation – Impurity Tracking The Impurities Lifecycle Management system establishes a knowledgebase of project impurities and elution data that results from method development using ACD/AutoChrom and data interpretation with ACD/SpecManager. Sample ID and spectra are stored with peaks and methods. As new injections are performed, Automation Server processes this data, establishing a Peak Query Function for each peak. Previously-identified components are automatically assigned, while novel (or questionable) peaks are highlighted for analyst attention. The peak query function combines searches based on method, retention time, and spectral response, proposing one or more sample IDs for each peak. The result is dramatically improved efficiency of data review, often avoiding redundant impurity identification. Instrument Data Project Impurities Elucidation Workflow Peak Query Macro Automation Server Previously Observed New Components Data Archive C H3 C H3 O O H CH O O CH3 CH3 CH3 3 OH Figure 4: As impurities for a given project are identified their spectra are appended to the chromatogram and uploaded to the knowledgebase. The peak query function can be applied to every new peak associated with the project. Conclusion Systems designed for automated creation of chromatographic knowledgebases, as an offshoot of normal business activities, help to streamline chromatographic method development, method selection, and data interpretation. References 1. F. Riley and M. McBrien, Efficient Chiral Screening and Purification in Support of Medicinal Chemistry, NMCS 2006, available at www.acdlabs.com/resources/ 2. T. Ponzio, Efficient Development of Chiral Chromatographic Methods, Pittcon 2008, available at www.acdlabs.com/resources/ 3. John D. Stafford, Todd D. Maloney, David P. Myers, Jose M. Cintron, Bryan C. Castle, A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis, Journal of Pharmaceutical and Biomedical Analysis, 56(2):280–292, 2011. 4. G. Xue, J. Harwood, Y. Xiang and M. McBrien, A. Vazhentsev, Building a Global Chromatography Knowledgebase for Method Development Prediction, HPLC 2009, available at www.acdlabs.com/resources/ 5. M. McBrien, D. Synderman, G.A. McGibbon, Collaborative Sample Elucidation Impurity Tracking and Identification, EUM 2009, available at www.acdlabs.com/resources/ Advanced Chemistry Development, Inc. Tel: (416) 368-3435 Fax: (416) 368-5596 Toll Free: 1-800-304-3988 Email: [email protected] www.acdlabs.com
Transcript of Organisational Learning in Chromatography · Organisational Learning in Chromatography Mike...
Organisational Learning in Chromatography
Mike McBrien, Andrey Vazhentsev, Dima Tzarev, and Susan Ling
Advanced Chemistry Development, Inc., (ACD/Labs),
Toronto, Ontario, Canada
IntroductionChromatography is a popular analytical technique used in organisations across a wide range of chemistry-related endeavours. Chromatographic results collected from different instruments are typically segmented and therefore contribute very little to organisational learning. In order to establish a true chromatographic knowledgebase, it is necessary to store and relate processed data to its chemical context. When established, a chromatographic knowledgebase can form the backbone of systems for chromatographic prediction and method selection, and facilitate interpretation of new samples.
Data �lesMolecule
Registries dbLaboratoryNotebooks
ELNs
Reports
Figure 1: The silos that typically separate chromatographic knowledge in an organisation.
ArchitectureA chromatographic knowledgebase must not only include chromatographic data, but also relate that information to its chemical context. The critical aspects of this context can be subtly different depending on the proposed application, but can be generalized as the interpretation of the data. Chemical context may include sample names, spectral-peak assignments, or structures linked to elution data with methods. ACD/SpecDB and ACD/ChromGenius are knowledgebases that are designed to relate stored chromatographic data, including spectra, components, and chromatographic peaks, to their chemical context, such as structures, elution tRs, and chromatographic methods, respectively.
AutomationIt is rare in modern business to have the luxury of dedicated instruments and systems to automate the routine of chromatographic work and establish even the most critical of efficiency systems. Any workflow designed to accumulate knowledge must be an offshoot of an analysis that is already being done, and require little to no manual effort on the part of the chromatographer. Ideally, the accumulation should be part of an approach to increase the accuracy and efficiency of the primary objective.
ACD/AutoChrom’s method development system and ACD/Automation Server’s scripting engine are designed to automatically store the data collected and interpret the analytical information. Component detection and identification results can be generated more efficiently, and transferred to the knowledgebase in the background, with little to no additional effort on the part of the analyst. In both cases, the primary goal of automation is the streamlining of day-to-day operations.
Leveraging the Knowledge1. Chiral Method Selection
The Automated Chromatographic Application Databasing System (ACADES) is a method development solution particularly suited to chiral methods. Chiral screening results are automatically reviewed and linked to chemical structures and methods. Reports are automatically generated, and the results (positive and negative) of each screen are passed to the knowledgebase. The screens then form the basis of structure-based method prioritisation, reducing the number of experiments required for new samples.
Storage Network
File Archive (raw or processed data)
SpecDB
AutomationServer
Macro
DocumentManagement
Figure 2: ACADES applied to chiral method development. Storage of screening results provides the basis for structure-based prioritisation of screens for new samples.
2. Achiral Generic Method Selection
Both ACADES and AutoChrom can be applied to create a knowledgebase for the prediction of elution in achiral methods. In this case, explicit prediction of elution (as opposed to selectivity) is possible through the ChromGenius application. Once established, it is possible to enter one or more structures, and generate predicted chromatograms for all generic methods.
Sample CreationStructure/Retention
Knowledgebase
MethodSelection System
Training
Cl
O OCH3
Cl
O OCH3tR
Figure 3: Structures attached to peaks, arranged by method, provide the basis for ChromGenius’ prediction of new chromatograms and subsequent method selection.
3. Sample Interpretation – Impurity Tracking
The Impurities Lifecycle Management system establishes a knowledgebase of project impurities and elution data that results from method development using ACD/AutoChrom and data interpretation with ACD/SpecManager. Sample ID and spectra are stored with peaks and methods. As new injections are performed, Automation Server processes this data, establishing a Peak Query Function for each peak. Previously-identified components are automatically assigned, while novel (or questionable) peaks are highlighted for analyst attention. The peak query function combines searches based on method, retention time, and spectral response, proposing one or more sample IDs for each peak. The result is dramatically improved efficiency of data review, often avoiding redundant impurity identification.
InstrumentData
ProjectImpurities
Elucidation Work�ow
Peak Query Macro
AutomationServer
PreviouslyObserved
NewComponents
Data Archive
CH3
CH3
O
OH
CH
O
O
CH3CH3
CH3
3
OH
Figure 4: As impurities for a given project are identified their spectra are appended to the chromatogram and uploaded to the knowledgebase. The peak query function can be applied to every new peak associated with the project.
ConclusionSystems designed for automated creation of chromatographic knowledgebases, as an offshoot of normal business activities, help to streamline chromatographic method development, method selection, and data interpretation.
References1. F. Riley and M. McBrien, Efficient Chiral Screening and Purification in Support of
Medicinal Chemistry, NMCS 2006, available at www.acdlabs.com/resources/
2. T. Ponzio, Efficient Development of Chiral Chromatographic Methods, Pittcon 2008, available at www.acdlabs.com/resources/
3. John D. Stafford, Todd D. Maloney, David P. Myers, Jose M. Cintron, Bryan C. Castle, A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis, Journal of Pharmaceutical and Biomedical Analysis, 56(2):280–292, 2011.
4. G. Xue, J. Harwood, Y. Xiang and M. McBrien, A. Vazhentsev, Building a Global Chromatography Knowledgebase for Method Development Prediction, HPLC 2009, available at www.acdlabs.com/resources/
5. M. McBrien, D. Synderman, G.A. McGibbon, Collaborative Sample Elucidation Impurity Tracking and Identification, EUM 2009, available at www.acdlabs.com/resources/
Advanced Chemistry Development, Inc.Tel: (416) 368-3435 Fax: (416) 368-5596
Toll Free: 1-800-304-3988Email: [email protected]
www.acdlabs.com
