Degradation identification

Capillary HPLC-MS has been reported as a confirmatory tool for the analysis of synthetic dyes [585], but has not been considered as a general means for structural information (degradant identification, structural elucidation or unequivocal confirmation) positive identification of minor components (trace component MW, degradation products and by-products, structural information, thermolabile components) or identification of degradation components (MW even at 0.01 % level, simultaneous mass and retention time data, more specific and much higher resolution than PDA). Successful application of LC-MS for additive verification purposes relies heavily and depends greatly on the quality of a MS library. Meanwhile, MB, DLI, CF-FAB, and TSP interfaces belong to history [440]. 

Manufacturing identification Impurity and degradant identification Identification and quantitation No Low... 

Manufacturing Sales Compliance Impurity and degradant identification. 

Formulation Degradant identification Predictive models for chemical degradants Predictive models for biomolecule degradants Rourick et al., 1997 Kleintop et al., 1998... 

Legal/patent protection Impurity/degradant Identification Impurity profiling Eckers et al., 1997... 

Procedure or forms for investigating, reporting, corrective action Forced degradation/stress studies Material to be tested Conditions Extent of degradation Identification of degradants Switch to ICEI conditions Allowable circumstances Procedure... 

Curing reactions Vulcanisation reactions Isothermal ageing Product stability Thermal degradation Identification of processing aids Plasticisers Mould lubricants Blowing agents Antioxidants Flame retardants Safety concerns... 

The strategy for impurity and degradant identification described by Rourick et al. subjects lead candidates to various development conditions followed by LC/MS and LC/MS/MS analysis protocols. A structure database is constructed from the corresponding results and is used to reveal unstable regions within the drug structure as well as to ascertain which candidate or homologous series of drug candidates may be the most favorable for further development. 

FIGURE 8 Global perspective of the purposeful degradation, identification, and method development process. 

Now that we know what some of the tools are, the following will illustrate the utility of mass spectrometry in the arena of impurity/degradant identification using these tools. Recognize that we have left out a large variety of very valuable and interesting areas and aspects of mass spectrometry to focus on the analysis of pharmaceutically important compounds. 

Manufacturing Marketing sales Compliance 1- Impurity 2- Degrading identification... 

Aerobic degradation in soil, initial study and further studies including the rate and route of degradation, identification of the processes involved, identification of any metabolites and degradation products in at least three soil types Field soil dissipation and accumulation Extent and nature of bound residues... 

Thermal degradation Identification of polymers Determination of thermal stability Evaluation of antidegradants... 

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