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Diagnostic: "Pseudo internal standard"
Internal standardization can improve precision when the dominant sources of error are related to sample preparation or injection; because such errors affect both the internal standard and the analyte peak in the same way, they will tend to cancel out when the ratio of areas is calculated. Internal standardization can degrade precision when the dominant sources of error are related to separation, peak shape, or integration; because such errors affect the internal standard peak and the analyte peak differently, they will tend to combine when the ratio of areas is calculated. Even if your method does not use an internal standard, you can use this to help identify the source of precision problems, so long as your chromatograms have at least two peaks of comparable size. 

Calculate the ratio of peak areas (or peak heights) for two peaks on the chromatogram. Compare the precision of this area ratio to the precision of the areas.
  • If the area ratio is more precise than the areas, the dominant source of error is probably "upstream" of the separation: injection, dilution, sample preparation, etc. 
  • If the areas are more precise than the area ratio, the dominant source of error is probably "downstream" of the injector: separation, baseline noise, peak shape, integrator settings, etc.
     


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