Aspirin degradation products

As the following pages of this section will show, there is hardly a new method of analysis which is not immediately tried for the determination of aspirin as such, or in formulations and biological fluids. The analysis of aspirin is intricately interwoven with that of salicylic acid, its precursor and degradation product. From the very first, residual salicylic acid was determined by the convenient reaction with ferric salts — typical for phenols — which give a violet complex with salicylic acid. 

The application of a ruggedness test to the assay of Aspirin and its major degradation product, salicylic acid... 

The first case study we will consider is the assay of aspirin together with its major degradation product salicylic acid [19], This application study was selected as the HPLC assay of aspirin is well covered in the literature and we could select factors to test from the variety of HPLC conditions used in these published methods. This test was performed using a reflected saturated factorial design requiring a total of 15 experiments. 

An investigation of degradation products was published in 1990 by Drennen and Lodder [88]. The major degradation process in aspirin tablets is the hydrolysis of aspirin to salicylic acid. One of two accepted United States Pharmacopeia (USP) methods must be performed to verify tablet aspirin content. A second HPLC analysis is performed to verify that salicylic acid levels do not exceed 0.3%. 

Blondino, F.E. Byron, P.R. The quantitative determination of aspirin and its degradation products in a model solution aerosol. J.Pharm.Biomed.Anal., 1995, 13, 111-119... 

Salicylate, which is a degradation product of aspirin in the human, is lipid soluble and has a dissociable proton. In high concentrations, as in salicylate poisoning, salicylate is able to partially uncouple mitochondria. The decline of ATP concentration in the cell and consequent increase of AMP in the cytosol stimulates glycolysis. The overstimulation of the glycolytic pathway (see Chapter 22) results in increased levels of lactic acid in the blood and a metabolic acidosis. Fortunately, Dennis Veere did not develop this consequence of aspirin poisoning (see Chapter 4). 

Fung et al. (44) studied the interaction of bilirubin, a product of heme degradation, with HSA by frontal analysis. They examined especially the displacement of bilirubin by aspirin. It was found that the free-bilirubin concentration increased to a clinically signihcant level when increasing amounts of aspirin were added. 

The base used in the formulation of suppositories can often affect the rate of decomposition of the active ingredients. Aspirin decomposes in several polyoxyethylene glycols which are often incorporated into suppository bases. Degradation was shown to be due in part to transesterification, giving the decomposition products salicylic acid and acetylated polyethylene glycol. The rate of decomposition, which followed pseudo first-order kinetics, was considerably greater than when a fatty base such as cocoa butter was used. Analysis of commercial batches of 100 mg indometacin-polyethylene glycol... 

To meet the speed and high efficiencies in separations demanded by the pharmaceutical industry, combined HPLC methods have been frequently used to simultaneously determine combination products [67]. A stability-indicating method for the simultaneous determination of aspirin and warfarin in warfarin sodium/aspirin combination tablets has been recently developed and validated [68]. In another example [69], the simultaneous determination of enalapril (2) and its two degradants, enapril-DKP (3) and enalapril-diacid (4), and felodipine (5) and its degradant, named HI52/37 (6) was achieved using combined method approach. 

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