| Abstract
| - The present study proposes a general method for constructing pharmaceutical fingerprints in the analysis ofHPLC trace organic impurity patterns. The approachconsiders signals in phase space and accounts for twodifferent types of noise: additive and perturbative. Thefirst type, additive noise, contributes to distortion of theabsolute values of signal peaks. The second type, perturbative noise, contributes to variations of the retentiontimes of signal peaks and distorts the time scale of thetrace organic impurity patterns. The ability of the proposed approach to consider both types of noise significantly distinguishes it from existing methods of dataanalysis that are usually designed to treat only the additivenoise. Analysis of the HPLC signals in phase spaceeliminates the problem of perturbation noise and enablesdetection and comparison of similar signal segmentsrecorded at different retention times. The current studyanalyzes the chromatographic trace organic impuritypatterns collected from six different manufacturers ofl-tryptophan using three HPLC columns. For five manufacturers the variability of data recorded with the samecolumn are in perfect agreement with the proposed model.A significant variance of parameters is detected for onemanufacturer, thus indicating a possible change in itsproduct consistency. The analysis in phase space is alsoused to explain the previously detected variability of HPLCsignals across columns. The accompanying paper reportsan application of the proposed approach for the patternrecognition of HPLC data.
|
