Stability-indicating method stress testing

The stress studies should demonstrate that impurities and degradants from the active ingredient do not interfere with the quantitation of the API [12]. Stress testing of the API, in addition to validating the stability-indicating power of the analytical method, can also help establish the degradation pathways and the intrinsic stability of the molecule [7]. 

Stress testing is an important part of the drug development process as it provides knowledge about the degradation chemistry of drug compounds. This knowledge is used primarily to develop stability-indicating analytical methods but is also useful for other purposes such as formulation develop-... 

Li, Y. G., Liu, H., and Wang, Z. T. 2005c. A validated stability-indicating HPLC with photodiode array detector (PDA) method for the stress tests of Monascus purpureus-fermented rice, red yeast rice. J. Pharm. Biomed. Anal. 39(1-2), 82-90. 

If the method is stability indicating, this should be demonstrated by stress-test data, measured during method-development. 

The decision to test is usually driven by unusual chemistry such as a new catalyst, reaction components, or reaction conditions. Immersion/mass loss method is primarily used in conjunction with microscopic examination. Process fluids from production or pilot runs are primarily used to best simulate potential corrosion. The test methods are custom designed based, in part, on cost and the ability to obtain sufficient quantities of test fluids, and handle the process conditions. Process conditions are tested outside the process control limits (e.g., temperatures, pH) to better accentuate the corrosion potential. These extremes have to be tempered by the stability of the products in the stream. For wall thicknesses greater than 0.250 in. (6.35 mm), a uniform loss of less than 10 mil/year (0.26 mm/year) is considered structurally acceptable. Signiflcandy lower levels of uniform loss are of concern for product or process contamination issues. Microscopic examination is used to determine potential localized corrosion concerns, such as pitting or stress cracking. Indications of pitting or stress corrosion in stamped areas of the coupon are of particular concern. U-bend tests are rarely used because of insufflcient test fluid quantities and availability. 

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