Chemical degradation pathways

The first discovery of certain enzymes and metabolites in chemical degradation pathways. 

The hydrolysis reaction of pentazocine is the only chemically degradative pathway which has been observed. An early report described the reaction and characterized the product 1,2,3 4,... 

Formulation scientists must consider two types of stability chemical and physical. Physical stability is the change in the physical form of the drug—for example, an amorphous form changing into a crystalline form. The chemical composition remains the same as it was prior to crystallization, but the drug now has different physical properties. Chemical stability is a change in the molecular structure through a chemical reaction. Hydrolysis and oxidation are two common chemical degradation pathways. 

Other chemical degradation pathways include -elimination, which can lead to racemization and disulphide exchange reactions. The amino acids that may undergo P-elimination include Cys, Ser, Thr, Phe, and Lys (40) and occur especially at alkaline pH (64). The reduction and oxidation of the disulphide bonds are often accompanied by a considerable change in the protein conformation (23,33). An example is the secondary structure of insulin that is disrupted or completely lost when the disulphide bonds are broken (23). The disulphide bond disruption or interchange can also result in an altered three-dimensional structure and therefore a possible loss of activity (40) or aggregation (29). For further details, the reader is directed to the following reviews and book chapters (30,40,62,65). 

In the previous section, the chemical degradation pathways for many drug substances were classified according to various pathways and mechanisms. In this section, factors that affect the rates of chemical degradation are elaborated. 

The major known chemical degradation pathways for peptides and proteins are deamidation, racemization, isomerization, hydrolysis, disulfide formation/exchange, P-elimina-tion, and oxidation. 

Oxidation. Oxidation is an important chemical degradation pathway for several proteins and can occur during all steps of its pharmaceutical development. The amino acids that are labile to oxidation are Met, His, Cys, Trp, Phe, Tyr, and Pro. Met has been identified as one of the most easily oxidized amino acids in proteins... 

Study of the chemical degradation pathways of penicilloic acid (Levine 1960b,c Schwartz 1969) (see Fig. 5) suggested that penicilloic acid interacts with... 

To analyze the passage of a chemical through the environment, data are required on the biodegradation, photodegradation, and chemical degradation pathways, as well as on its physical and chemical properties. These data help to determine the removal of a chemical from the environment and its conversion into other breakdown products. 

Chemical or Covalent Degradation of Proteins. Proteins are subject to a variety of chemical modification and degradation reactions such as hydrolysis, deamidation, isomerization, disulfide reshuffling, -elimination, and oxidation (Table 1) (13,14). The stability of proteins toward chemical degradation pathways often depends on the protein s folded state. In order for the chemical reactions to occur, the labile residue must be solvent accessible and must have varying degrees of structural freedom of the peptide backbone and/or side chains around the labile residue. Hence, stabilization of the protein s folded state (ie, its compact structure) that minimizes solvent accessibility and rotational freedom can lower the reaction rate of some chemical degradation reactions. 

DePaz R, Barnett CC, Dale DA, Carpenter JF, Gaertner AL, Randolph TW.The excluding effects of sucrose on a protein chemical degradation pathway methionine oxidation in subhUsin. Arch Biochem Biophys 2000 384 123-32. 

Ultrasound plays a role in either the chemical degradation pathway or the electrochemical reaction at the electrode based on the frequency used. The increase extent is closely related with the electrode material. It seems that further investigation of the geometry of both electrodes and reactor is needed in order to optimize the ultrasound energy distribution, enhance the degradation efficiency, and reduce the energy consumption. 

Although studies on the degradation mechanism of SL-950 have just been started, judging from the fiu t that SL-950 has almost same dissociation constant (pKa 4.6) as SL-160, 81 950 is expected to follow a similar chemical degradation pathway. The short-residual properties of SL-160 have been described in the chapter of Haga et al. If 81 950 behaves similarly in soil, it will have a persistence profile that is very attractive for rotational cropping. Such properties may be considered important for future sulfonylurea herbicides. 

Assadi AA, Palau J, Bouzaza A, Wolbert D (2013) Modeling of a continuous photocatalytic reactor for isovaleraldehyde oxidation effect of different operating parametras and chemical degradation pathway. Chem Eng Res Des 91 1307-1316... 

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