Impurities/degradants isolation and identification

FIGURE I Impurity/degradant isolation and Identification process flowchart (RRT relative retention time PRI = process-related impurity). 

FIGURE 2 Impurity/degradant isolation and identification process flowchart. 

FIGURE 9 Impurity/degradant isolation and identification process flow chart. PRI, process-related impurity STD. standard RRT, relative retention time MW, molecular weight. 

Interpretation of the spectroscopic data from the individual spectroscopic techniques is generally done as the data are amassed. When all of the data are available, it is useful for the participating scientists to integrate their respective data, which is discussed in more detail below. The overall elapsed time for the isolation and identification of a new impurity or degradation product is quite variable. The difficulty of the actual isolation and the structural complexity of the molecule both impinge on the process. On the basis of the author s experience. 

One of the challenges inherent to working in this area of structure characterization is that when an impurity is observed, it is difficult to quantitate the impurity present when the structure is unknown. Regulatory guidelines mandate the isolation and identification of impurities or degradants present at >0.1% in most cases unless the drug is dosed at very high levels, but until the chromophore of the molecule is identified and evaluated, it is difficult to determine whether or not the... 

Alsante, K.M. Hatajik, T.D. Lohr, L.L. Sharp, T.R. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates, part I. Am. Pharm. Rev. 2001, 4 (1), 70-78. 

Isolation and identification of process related impurities and degradation products from pharmaceutical drug... 

The next step is to determine at what level the unknown impurities are present. Identification of impurities below the 0.1% level is generally not necessary unless the potential impurities are expected to be unusually potent or toxic. Therefore, it is imperative to determine the level of the unknown impurity and/or degradation product early in the process. If the unknown is at or above the 0.1% limit, effort should be made to identify it. However, if the unknown is below the 0.1% threshold, a discussion should be conducted with the project team members to determine if isolation and identification are necessary. 

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