Pharmaceutical agents antineoplastics

In addition to antineoplastic, cytotoxic agents, there are cancer therapeutic or preventative drugs that are intended to be given on a chronic basis. This includes chemopreventatives, hormonal agents, immunomodulators, and so on. The toxicity assessment studies on these will more closely resemble those of more traditional pharmaceutical agents. Chronic toxicity, carcinogenicity, and Ml developmental toxicity (ICH A-B, C-D, E-F) assessments will be required. For a more complete review, the reader is referred to DeGeorge et al. (1998). 

Alkyl halides, alkyl sulfonates and other alkylating agents have also been subject to scmtiny in spheres other than pharmaceuticals, such as in environmental analysis. Various approaches have included two-step SPE, derivatisation with trifluoroacetic anhydride followed by GC/MS (for cyclophosphamide and its analogues in sewage water) SPE on surface water to isolate the antineoplastic agents carmustine, chlorambucil, cyclophosphamide and melphalan for LC-UV and LC-fluorescence measurements and derivatisation of alkyl halides and epoxides with 4-nitrothiophenol followed by HPLC-UV detection (claimed to be better than NBP derivatisation). A patent exists for a field test kit for mustard gases in military use based on NBP derivatisation. 

One should consider that plant-derived steroids alone account for about 15% ( 22 billion) of the 150 billion world pharmaceuticals market and that the annual market for taxol exceeded 1 billion in the year 2000. The antineoplastic agents vinblastine and vincristine have sales amounting to 100 million per year the market for psyllium seed products amounts to some 300 million annually and nicotine and scopolamine patches now have combined sales of more than 1 billion per year. It is obvious that natural products continue to play important economic as well as therapeutic roles in modem medicine. 

Urethane may be released to the environment in various waste streams from its production and use in the preparation and modification of amino resins, as a solubilizer and cosolvent for pesticides and fumigants, as an intermediate in the production of pharmaceuticals, as an antineoplastic agent, and as a reagent in biochemical research. If released to the atmosphere, urethane is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase urethane will be degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals with an estimated half-life of 2.2 days. If released to soil, urethane is expected to have very high mobility. Volatilization from moist soil surfaces is not expected to occur. Biodegradation of urethane in soil may be important. If released into water, urethane is not expected to adsorb to suspended solids and sediment in the water column. Volatilization from water surfaces is not expected. The potential for bioconcentration in aquatic organisms is... 

Leslie M. Werbel, Donald F. Worth, and Sarah M. Weitzel, Warner-Lambert I Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan Antineoplastic Agents... 

Pteridines are also used as pharmaceuticals. Triamterene 15 is a diuretic that promotes excretion of Na" and retains K+. The folic acid antagonist methotrexate 16 (amethopterin) is of considerable importance as an antineoplastic agent in cancer chemotherapy. 

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