Pharmaceuticals transformation products

Organophosphate flame retardants and plasticisers Perfluorinated compounds Pharmaceuticals and personal care products Polar pesticides and their degradation/transformation products Surfactants and their metabolites... 

J. Brange, S. Havelund, and P. Hougaard, Chemical stability of insulin 2 Formation of higher molecular weight transformation products during storage of pharmaceutical preparations, Pharm. Res, 9, 727 (1992). 

Keywords Degradation, Pharmaceuticals, Toxicity, Transformation products, White-rot fungi... 

Shooty teratomas are differentiated cell cultures produced by transformation with certain strains of A. tumefaciens [107]. Thus far, there has been only one report of pharmaceutical protein production in teratoma cultures, and the levels of antibody were very low [106]. 

Zwiener C. (2007). Occurrence and analysis of pharmaceuticals and their transformation products in drinking water treatment. Analytical and Bioanalytical Chemistry 387 1159-1162. 

Matyus et al. reported the synthesis and cardiotonic activity of pyrimido[5,4-6][l,4]oxazinones <90JHC151>. The synthesis started from 6-amino-2,3-dimethyl-4(3//)-pyrimidinone. Also 4-sub-stituted pyrimido[5,4-6][l,4]oxazinones were transformed into pharmaceutically interesting products. Several compounds were prepared some showed an ionotropic effect, for example (208) and (209). 

So far, the main focus of multimedia fate models has been on single chemicals, but extensions may become available to include fate of transformation products. This may open the way to making the models applicable to mixtures (OECD 2004). Initially such development may simply be made through the serial analysis of the fate of individual chemicals, and from this a derivation of probable concentrations of each, assuming no interaction. Such analysis is, for example, feasible for many of the most widely used down the drain and is at present being extended to other product types, such as personal care chemicals and human pharmaceuticals. Such combined analysis would in fact represent a considerable step forward in addressing the nature of likely mixture exposures however, if the interactions with the environment and between chemicals as outlined above are to be considered, then this would require a considerable effort to understand and include the major processes involved within existing models. 

Perfluoroalkylated substances and their transformation products Personal care products Petrol additives Pesticides Pharmaceuticals... 

Degradation processes, particularly in drinking water treatment processes, may result in transformation products that may be of greater health concern than the parent compound. For example, some pharmaceuticals with amine functionality are possible precursors for nitrosamines—which can be mutagenic and carcinogenic. ... 

Abstract This chapter gives an overview of strategies used in the identification and analysis of environmental transformation products of three important groups of synthetic chemicals pesticides, pharmaceuticals, and personal care products. The characteristics and features of modern mass spectrometric instrumentation coupled to liquid chromatographic separation techniques as well as complementary techniques are presented and examples of their application to the characterization of transformation products of synthetic chemicals are described. Analytical methodologies for the quantitative analysis of the intact parent compounds and their transformation products in the environment are compiled. 

Whereas studies on the environmental photochemistry of the majority of pesticides have been conducted extensively, few data exist for PPCPs. Pharmaceuticals are mainly polar compounds containing acidic or basic functional groups (such as carboxylic acids, phenols, and amines) that may be subject to direct and indirect photolysis. Although microbial degradation in waters and soil has been reported for pesticides, less work is reported for PPCPs. The result of such processes can be a complex mixture of reactive intermediates and TPs. Their identification represents a more challenging task than the identification of transformation products stemming from microbial transformation, for which at least some common mechanisms are well established. Therefore, the application of advanced instrumental techniques is of crucial importance. 

Except for pesticides, some high-production-volume chemicals and, more recently, some pharmaceuticals and biocides, measured half-hves are usually scarce. Experimental half-hves for transformation products, except for soil half-hves of some well-known pesticide transformation products, are usually not available. Therefore most of the degradation information entered into multispedes multimedia models is estimated. 

Both tools additionally suffer from the small number of reliable biodegradation studies in which transformation pathways were elucidated in enough detail to serve as training data for rule development and prioritization. Especially when confronted with compounds such as current-use pesticides and pharmaceuticals, both tools are lacking some of the rules necessary to break down these more complex molecular structures. Hopefully this situation will improve in the future since with the implementation of REACH, which requests identification of relevant transformation products for all compounds produced in amounts exceeding 100 t/year, the experimental biodegradation database is expected to grow considerably. 

Vogna et al. (2004) showed that UV/H2O2 (as well as molecular ozone) was effective at oxidizing transformation products of the pharmaceutical, diclofenac. Lau et al. (2007) studied the formation of a suite of ten transformation products of butylated hydroxyanisole by including 1,4-benzoquinone, f-butyl-l,4-benzoquinone, and hydroquinone. Some of the degradates were precipitated from solutions as an orange-colored solid that could be removed by filtration. The study showed that UV/ozone and ozonation were more effective than UV alone at removal of the parent and transformation products. 

As discussed earlier extensive data are available on the ecotoxicological effects of pesticide transformation products whilst only limited ecotoxicological data are available on the ecotoxicity of transformation products of other classes of compound such as human and veterinary pharmaceuticals, industrial chemicals and biocides. Generally transformation products are considered to be less toxic to non-target organisms, however some exhibit an equivalent or increased potency when compared to the parent compound. Therefore, in the following sections we take data on the aquatic (daphnid) and terrestrial (earthworm) ecotoxicity of pesticide transformation products and compare this to data on the ecotoxicity of the associated parent pesticide in order to explore the relationships between parent and transformation product ecotoxicity in aquatic and terrestrial systems. 

Most work on transformation product ecotoxicity has been done on transformation products of pesticides. While some data are available for other transformation products (e.g. veterinary medicines, industrial chemicals and pharmaceuticals), these data are quite limited. We should begin to assess the effects of transformation products from these other groups and establish whether the relationships described in this chapter for pesticides hold true for the wider chemical universe. 

Keywords Baseline toxicity Ecotoxicology Environmental transformation products Metabolites Mode of toxic action Pharmaceuticals Pesticides Herbicides QSAR... 

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