Preclinical stage of drug development

Since drug development has turned into a systematic and rational task of optimizing molecules and their interactions with proteins, cells, and organisms, combinatorial chemistry has become a significant part of this endeavor. Combinatorial methods are mainly employed in the initial (preclinical) stages of drug development. 

The preclinical stage of drug development focuses on activities necessary for filing an IND/CTA. The completed IND/CTA contains information that details the drug s composition and the synthetic processes used for its production. The IND/CTA also contains animal toxicity data, protocols for early phase clinical trials, and an outline of specific details and plans for evaluation. Process research, formulation, metabolism, and toxicity are the major areas of responsibility in this development stage. Analysis activities that feature LC/MS primarily focus on the identification of impurities, de-gradants, and metabolites. 

During the preclinical stage of drug development, speed and sample consumption are typically the most important factors when selecting a technique however, as the compound moves through the... 

When a pharmaceutical is in the early stages of drug development (e.g., preclinical phases), the amount of material is limited and little is known about the characteristics of the molecule. Thus, CE is an attractive technique for developmental work due to its low sample consumption. Multiple injections can be made from a few microliters of sample, thus allowing optimization and early qualification of methods. 

The search for new pharmacological treatments in psychiatry is intense and productive. Several dozen pharmaceutical companies are currently involved in various stages of drug development, and the next few years will see several new medications available for prescription. Altogether, more than 100 medications have completed the preclinical stage and are now in phases I, II, and III of clinical development (see Table B.l). 

SETTING SPECIFICATIONS AT DIFFERENT STAGES OF DRUG DEVELOPMENT A. Preclinical Studies... 

FIGURE 2.3 An overview of the drug development process that illustrates the activities within the four major stages of drug development drug discovery, preclinical development, clinical development, and manufacturing. (Courtesy of Milestone Development Services, Newtown, PA, 1998. With permission.)... 

Fig. 4.1 The distribution of human drug targets by protein family from (A) the 277 unique proteins enumerated as drug targets against the 1995 marketed human pharmacopoeia (adapted from [Drews and Ryser pullout]) and (B) the 374 unique proteins determined by the 2002 revised census to be the targets of all Lipinski rule-of-five compliant small molecule compounds in all stages of drug development from preclinical phases through the post-market (adapted from online Table 1 in...

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