Stability-Indicating Method SIM

The above statement has lot of details in reference to what is a SIM The statement starts with method validation (refer to Chapter 9). Next, most methods need to be specific (specificity, resolution of active from related substances, peak purity), reproducible (precision), quantitative (recovery, linearity, LOD, LOQ), and able to monitor a change in chemical, physical, and/or microbiological properties of drug products over time (refer to sections on stability testing and mass balance). 

Even if the same drug substance HPLC method is used for the drug product, forced decomposition studies must be performed again for the drug product to confirm the resolution of potential degradation products from the API. In addition, forced decomposition studies must also be performed for different dosage forms (capsule, tablet, suspension, injectable, etc.) of the same drug substance. 

Further in development, a combination product (capsule dosage form) of the development compound A with aspirin was proposed. The preformulation 

Time (minutes) Mobile Phase A Mobile Phase B Mobile Phase C Gradient 

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All of the background information discussed in the addendum (Common Functional Groups) will help an analytical chemist with development of a stability-indicating method (SIM) that will assist in the development of an optimized formulation that will become a drug product in the marketplace. Remember, an analytical chemist must be able to provide knowledge, not just data. 

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... 

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