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Sensitivity Enhancement in LC/MS
Our objective is to detail specific techniques to improve analytical response and diminish noise and interferences. We will generally track issues of “cause-and-effect” for each component along of the LC/MS analytical train from sample to detector and give specific alternatives.
I. Optimization of Analyte Response with LC/MS
A. Maximizing Analyte Response
1. Optimization of Ionization
a. Factors Affecting Ionization
i. Ionization Enhancement
ii. Ionization Suppression
b. Maximizing Ionization of Targets
i. Gas Phase vs Condensed Phase
2. Evaluating the Specificity of the Target Ion
3. Evaluating the Polarity of the Target Ion
4. Evaluating the Stability of the Target Ion
B. Eliminating Losses in LC/MS
1. Maximizing Analyte Recovery
2. Minimizing Source Losses
3. Minimizing Conductance Losses
4. Minimizing Transmission Losses
5. Duty Cycle and Trade-offs
II. Elimination of Interferences in LC/MS
A. Characterization of Interferences in LC/MS
1. Spectral Interferences
2. Chemical Interferences
3. Physical Interferences
4. Sources of Noise
B. Minimization of Spectral Interferences
1. Sample Prep and Chromatographic Solutions
2. Ion Mobility Solutions
3. Mass Spectral Solutions
C. Minimization of Chemical Interferences in LC/MS
1. Sample Preparation Solutions
2. Chromatographic Solutions
3. Ionization Solutions
D. Minimization of Physical Interferences
1. Minimizing Charging and Space-Charge Effects
2. Minimizing Aerosol Effects
3. Minimizing Positional Dependence
E. Minimizing Noise in LC/MS
1. Eliminating Background Noise
2. Elimination Source Noise
3. Statistics and Trade-offs
III. Development of Practical Methods for LC/MS
A. Protocols for LC/MS Methods Development
1. Methods for Quantitation
2. Methods for Target Analysis
3. Methods for ‘Unknowns’
4. Sample Preparation Approaches
B. Characterizing Sample Variability
C. Characterizing Solvent and Reagent Variability
1. Solvents for LCMS
D. Characterizing System Variability
E. Special Methods for Specific Classes of Compounds
1. Proteins
2. Peptides
3. Amino Acids
IV. Information from LC/MS
A. Mass Information
1. Accurate Mass
2. Unit Mass
B. Structural Information
1. Isotopic Distribution
2. Chemical Information
V. Other
A. Balancing Priorities
1. Time is Money
2. Rework is Money
3. Liability is Money
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[ 本帖最后由 aa_tang 于 2008-1-29 20:55 编辑 ]