Degradants products Impurities

Degradation Product, Impurities, and Chemical Composition Index... 

Note Mineralization and combustion products products (carbon dioxide, carbon monoxide, water vapor, and inorganic ions) are not included. Compounds listed include degradation products, impurities, and components in commercially available products (e.g., stabilizers, inhibitors, etc.). Refer to Appendix 1 for compounds that are underlined. 

There are several parameters which require critical consideration. Firstly, the colour reagent should be selective for the drug molecule itself, discriminating against degradation products, impurities, and formulation excipients likely to be present. Secondly, the effect and control of any parameters likely to affect the colour reaction should be established, i.e. 

Degradation products/impurities Reporting level to at least 120% of specification limit. 

Provisional RfDs and RfCs for 25 degradation products, impurities and stabilizers (Bausum, 1998) are listed in Table 5. These values can be compared with the estimated oral RfD for VX of 0.0006 qg/kg/day (Opresko et al., 1998). Where data were unavailable for a degradation product, but the mechanism of action for the chemical was the same or predicted to be the same as that of VX, the value for VX was assigned. Thus, although both EA 2192 and bis(,S, S-(diisopropylaminoethyl) methylphosphonodithi-olate are less toxic than VX, the conservative value of 0.0006 qg/kg/day value was proposed. Health-based soil screening levels for the parent compound range from 0.042 to 0.047 mg/kg of soil (US Army CHPPM, 1999). 

Details of the degradation products, impurities, stabilizers, etc. for the various evaluated chemical warfare agents discussed in this chapter are given in Tables A1-A6. 

Table A3. Degradation products, impurities, and stabilizers of agent VX ...

Simultaneous degradation products, impurities, benzaldehyde, benzyl alcohol, mometa-sone furoate, orthochlorophenyl-diphenylmethanol... 

Terephthahc acid is pure white, and molten dimethyl terephthalate is colorless. Impurities or degradation products can be yellow or brown, so the darkness of either a solution of terephthahc acid in dimethylform amide or molten dimethyl terephthalate can be compared to APHA color standards. 

In 1933, R. Kuhn and his co-workers first isolated riboflavin from eggs in a pure, crystalline state (1), named it ovoflavin, and deterrnined its function as a vitamin (2). At the same time, impure crystalline preparations of riboflavin were isolated from whey and named lyochrome and, later, lactoflavin. Soon thereafter, P. Karrer and his co-workers isolated riboflavin from a wide variety of animal organs and vegetable sources and named it hepatoflavin (3). Ovoflavin from egg, lactoflavin from milk, and hepatoflavin from Hver were aU. subsequently identified as riboflavin. The discovery of the yeUow en2yme by Warburg and Christian in 1932 and their description of lumiflavin (4), a photochemical degradation product of riboflavin, were of great use for the elucidation of the chemical stmcture of riboflavin by Kuhn and his co-workers (5). The stmcture was confirmed in 1935 by the synthesis by Karrer and his co-workers (6), and Kuhn and his co-workers (7). 

The guideline on impurities in new medicinal products parallels the drug substance text, but the designated thresholds concern only degradation products. The thresholds should be applied to the product at the end of its shelf-life, as that is when the greatest level of degradation is expected to have occurred. 

The quality of the product must meet high requirements of USP XXII and FDA regulations, considering high pharmacological activity of any present impurities. Therefore, the investigation of impurities and degradation products has absolutely been necessary. 

The analytical method must have been run using a variety of compounds that might turn up as impurities (synthesis byproducts, degradation products) to prove that there is sufficient selectivity. Materials in contact with the sample (tubing, filters, etc.) that might interfere with the analytes of interest must be proven to be innocuous. 

The objectives of the soil persistence experiments were (1) to learn the effect of soil type and concentration on the TCDD degradation rate, (2) to isolate and characterize degradation products from DCDD and TCDD, and (3) to determine whether chlorodioxins could be formed from chlorophenol condensation in the soil environment. This last study was essential since quality control at the manufacturing level could reduce or eliminate the formed dioxin impurity. But the biosynthesis of chlorodioxins by chlorophenol condensation in the soil environment could not be controlled and would have connotations for all chlorophenol-de-rived pesticides if formation did occur. The same question needed to be answered for photochemical condensation reactions leading to chloro-... 

Related substances are defined as known impurities which may be identified or unidentified (Technical Guide for the Elaboration of Monographs 1996). They include intermediates and by-products from a synthetically produced organic substance impurities, co-extracted from a natural product and degradation product of the substance. 

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