Stability-indicating method mass balance

Even if HPLC is chosen as the main stability indicating method, CE will be useful as orthogonal technique, especially in cases where the reason of mass balance deviations is unclear. In addition, due to its increased peak capacity and selectivity in comparison to HPLC, the detection of possible enantiomers, stereoisomers, and position isomers, having the same molecular weight and equal/similar spectra as the drug substance may be separated by a secondary CE method. 

A question often brought up in discussions of forced degradation and SIMs is whether mass balance should be achieved in all cases. Evidence that the total material detected in the stressed samples is equal to the starting input is certainly helpful for demonstrating the stability-indicating ability of the method. Mass balance results of 96-102% were reported for dipyridamole even with significant degradation of up... 

Forced degradation samples are used in the process of developing stability-indicating methods early in development prior to initiating formal stability studies. The samples are analyzed for API peak purity (coeluting impurities), specificity, and mass balance. Efforts are also focused on determination degradation pathways/mechanisms for API and DP. 

Mass balance is also useful in method validation (1,3,4). In order to demonstrate that analytical methods are stability indicating, unstressed and stressed materials are often compared. An increase in degradation products that correlates well with loss of parent drug aids in demonstrating that the methods can be used to accurately assess degradation. 

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