Drug stoichiometry

Methods have successfully been transferred to various laboratories in inter-company cross-validation exercises for a chiral separation, for an assay of the main component in a formulation and for drug stoichiometry. Revalidation is an alternative to method transfer in case of changes in product composition or analytical procedure (cf. Section I.L). Although a method transfer in CE is not a major difficulty, some aspects have to be considered, especially if a method is transferred to an instrument of another manufacturer. 

When the drug entity is capable of forming complexes that have higher stoichiometric ratios than 1 1, the construction of equilibrium constant expressions becomes more difficult. For the general case of m.n stoichiometry, as defined by... 

Quantitative determination of drug counterions stoichiometry chloride, sulfate... 

Thiolate ligands also afford an interesting variety of species [156-161]. Because or their relation with the antiarthritic drug Auranofin, thiolate-goldphosphine derivatives have received great interest. The simplest structures are those in which the thiolate bridges two gold atoms and thus different compounds of stoichiometry... 

A critical component of the G-protein effector cascade is the hydrolysis of GTP by the activated a-submit (GTPase). This provides not only a component of the amplification piocess of the G-piotein cascade but also serves to provide further measures of drug efficacy. The coupling process also depends on the stoichiometry of receptors and G-proteins, A reduction in receptor number should diminish the efficacy of coupling and dius reduce drug efficacy. 

Phase-solubility diagrams are frequently used to calculate stoichiometry of drug/CD complexes. 

Furthermore, ligand effects might be cell phenotype dependent. It is possible that the capacity of a receptor protein to adopt different conformations could be restricted when the receptor is in different microenvironments associated with different cells. Also, given different stoichiometries and quality of signaling molecules expressed in different cells, the same receptor conformation in different cells might signal differently. This makes it especially important that the system chosen for drug discovery be therapeutically relevant. 

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