Biological stability studies

The total quantity of ligand and macromolecule [Lo] and [Mo] is the sum of the free and bound ligand and macromolecule, respectively. Therefore Equation (15) can be re-written in terms oi[ML], [Mo] and [Lo], as Equation (16). 

Both [Mo] and [Lo] are known as [Mo] is the start concentration of the macromolecule and [Lo] is the sum of ligand added at each aliquot. It is possible, therefore, to plot [ML] as a function of [Lo], the total concentration of 

From Equation (17) an analysis can be made if the quantity of ML can be determined as a function of ligand added at each aliquot. However considerable errors may arise as this quantity must be assayed, after each aliquot of ligand is added. However non-invasive techniques such as isothermal microcalorimetry calorimetry can be used to directly determine the quantity of ML without disturbing the system. For a calorimetric analysis an estimation of the enthalpy change for the macromolecule-ligand interaction must be made. An assumption can be made that at the start of the study, the initial aliquot of ligand added to the system, if sufficiently small, will completely bind to the macromolecule (as initially the macromolecule will be in excess). The enthalpy change associated with this interaction can then be used to calculate the A// for the interaction (Equation (3)). 

Knowing AH, Equation (17) can be modified to Equation (18) so that the calorimetric response q) can be plotted as a function of ligand concentration Lo)  

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The plastic bottle and dispensing tip is made of low-density polyethylene (LDPE) resin, which provides the necessary flexibility and inertness. Because these components are in contact with the product during its shelf life, they must be carefully chosen and tested for their suitability for ophthalmic use. In addition to stability studies on the product in the container over a range of normal and accelerated temperatures, the plastic resins must pass the USP biological and chemical tests for... 

The physiochemically and biologically characterized proteins and peptides are further formulated and subject to stability studies. The goal of these studies is to develop a unique combination of excipients, solution pH, buffer, and container that will produce an optimum dosage form. Biopharmaceutical formulations should be... 

Microbial stability is one of the factors affecting drug product reliability. Under design and interpretation of stability studies, the Center for Drugs and Biologies... 

There are many examples, as cited above, which have demonstrated that the EC oxidation products for a given compound often coincide with metabolites observed in biological assays (Volk et al., 1988, 1989 Getek et al., 1989 Deng and Van Berkel, 1999 Jurva et al., 2000 van Leeuwen et al., 2005). These and other EC oxidation products may also be observed in purposeful degradation or stability studies. One must recognize, however, that enzyme-catalyzed, chemical and EC oxidations are often very complex and involve different phenomena. 

The rate of organic residue decomposition in soils and related environments is ultimately controlled by its biological stability, which is a function of the following four main factors, namely, (i) its biochemical recalcitrance, (ii) the biological capability and capacity of the environment, (iii) decomposition rate modifiers (e.g., temperature, moisture, exposure time) and (iv) physical protection mechanisms (Baldock et al., 2004). Recent studies have shown that the physical protection mechanisms, such as the spatial inaccessibility of organic matter in soil micropores, are the most important factors in controlling the stability of organic matter in soils (Mikutta et al., 2006 von Liitzow et al., 2006). 

The HPLC procedures reported in the literature (see Table V) were developed mainly for biological and stability studies, and they do separate Melphalan from its hydrolytic degradation products. 

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