Stability indicating assay

Stability of a drug substance and product is monitored throughout the development and clinical phases. This monitoring requires stability-indicating assay methodology, and this is a subject that is separate from performulation per se. In most instances, the major, feasible decomposition products are identified early [51], and as such it is known if the pathways are hydrolytic, oxidative, or photochemical. 

XRPD as a stability-indicating assay method When the phase identity, or degree of crystallinity (or lack thereof), of a drug substance is important to its performance in a drug product, XRPD can serve as a vital stability-indicating assay method. There is no doubt that XRPD can be validated to the status of any other stability-indicating assay, and that one can use the usual criteria of method validation to establish the performance parameters of the method. This aspect would... 

If a MAb was available that could differentiate between the native and denatured forms of a protein product, an ELISA could be used as a stability-indicating assay. The antibody could also be used for purification of the native molecule by removal of the denatured form.21 A MAb specific for the denatured protein can detect small amounts of the denatured protein in the presence of the native form.21... 

Hong, D. D. and Shah, M., Development and Validation of HPLC Stability Indicating Assays, Drug Stability Principles and Practices, 3rd ed., Marcel Decker, Inc., New York, 2000. 

A stability-indicating method is a validated quantitative analytical procedure that can detect the changes with time in the pertinent properties of the drug substance and drug product under defined storage condition. A stability-indicating assay method accurately measures the active ingredient(s) without interference from other peaks and is sensitive... 

Bretnall, A. E., Hodgkinson, M. M., and Clarke, G. S. (1997). Micellar electrokinetic chromatography stability indicating assay and content uniformity determination for a cholesterollowering drug product. /. Pharm. Biomed. Anal. 15, 1071 — 1075. 

Tabre H, Hussam-Eddine N, Mandrou B. 1984. Stability-indicating assay for phenylbutazone High-performance liquid-chromatographic determination of hydrazobenzene and azobenzene in degraded aqueous phenylbutazone solutions. J Pharm Sci 73 1706-1709. 

Example stability indicating assay for product which is expected to be susceptible to hydrolysis and oxidation. Only one degradate (A) is readily available. 

Credible pharmaceutical product expiration dates are obtained by rigorous, scientifically designed studies using reliable, meaningful, and specific stability-indicating assays, appropriate statistical concepts, and computers to analyze the resulting data [2]. A comprehensive review of all aspects of pharmaceutical product stability has been published by Lintner [3] and more recently by Connors et al. [4]. 

Bakshi M, Singh B, Singh A, Singh S. The ICH guidance in practice stress degradation studies on ornidazole and development of a validated stability-indicating assay. J Pharm Biomed Anal 2001 26 891-897. 

Hong D, Shah M. Development and Validation of HPLC Stability-Indicating Assay. In Drugs and the Pharmaceutical Sciences. New York Marcel Dekker, 2000 329-384. 

Wahbi et al. [32] used a spectrophotometric method for the determination of omeprazole in pharmaceutical formulations. The compensation method and other chemometric methods (derivative, orthogonal function, and difference spectrophotometry) have been applied to the direct determination of omeprazole in its pharmaceutical preparations. The method has been validated the limits of detection was 3.3 x 10 2 /ig/ml. The repeatability of the method was found to be 0.3-0.5%. The linearity range is 0.5-3.5 /ig/ml. The method has been applied to the determination of omeprazole in its gastro-resistant formulation. The difference spectrophotometric (AA) method is unaffected by the presence of acid induced degradation products, and can be used as a stability-indicating assay method. 

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