Partition absorption

The behavior of the nonpolar bonded phases, as well as the column packings based on crossbnked organic polymers of low polarity, however, differs from that of polar column packings and the classical solvent strength concept should be reevaluated. This is especially important for the alkyl bonded phases (Section 16.8.1). In this case, surface and interface adsorption of polymer species (Section 16.3.5) plays a less important role and macromolecules are mainly retained by the enthalpic partition (absorption) (Section 16.3.6). In order to ensure this kind of retention of polymer species, the mobile phase must push them into the solvated bonded phase. Therefore the interactions of mobile phase with both the bonded phase and (especially) with the sample macromolecules—that is, the solvent quality—extensively controls retention of latter species within the alkyl bonded phases. 

FIGURE 16.8 Schematic representation of enthalpic partition (absorption) of a macromolecule between the mobile phase and the (solvated alkyl) phase bonded on the silica surface. 

As stated in the Introduction, the most widely used LC separation mode for polymer analysis is SEC. For low molecular weight species, however, where separation of similar size molecules is required, interactive liquid chromatographic modes (partition/absorption) are more suited. 

Modified Freundlich sorption models were developed to describe sorption in heterogeneous geosorbents containing both NOM and carbonaceous materials. Composite or distributed reactivity models (DRM) were introduced [28] and applied in a manner which combines the linear partitioning (absorption) part with the nonlinear adsorption part [26, 27, 31, 32]. The overall sorption isotherm can be described in the form of ... 

Antioxidants have been shown to improve oxidative stabiHty substantially (36,37). The use of mbber-bound stabilizers to permit concentration of the additive in the mbber phase has been reported (38—40). The partitioning behavior of various conventional stabilizers between the mbber and thermoplastic phases in model ABS systems has been described and shown to correlate with solubiHty parameter values (41). Pigments can adversely affect oxidative stabiHty (32). Test methods for assessing thermal oxidative stabiHty include oxygen absorption (31,32,42), thermal analysis (43,44), oven aging (34,45,46), and chemiluminescence (47,48). 

Other important determinants of the effects of compounds, especially solvents, are their partition coefficients, e.g., blood-tissue partition coefficients, which determine the distribution of the compound in the body. The air-blood partition coefficient is also important for the absorption of a compound because it determines how quickly the compound can be absorbed from the airspace of the lungs into the circulation. An example of a compound that has a high air-blood partition coefficient is trichloroethane (low blood solubility) whereas most organic solvents (e.g., benzene analogues) have low air-blood partition coefficients (high blood solubility). 

Drugs that are too highly hydrophilic are often absorbed rather poorly from the gastrointestinal tract. It is sometimes possible to circumvent this difficulty by preparing esters of such compounds so as to change their water lipid partition characteristics in order to enhance absorption. Once absorbed, the esters are cleaved by the numerous esterase enzymes in the bloodstream, releasing free drug. 

The mechanism responsible for improved delivery of lipophilic drugs has not yet been clarified. Absorption of liposomes by cells is unlikely. Adsorption to cells followed by slow release of the drug from the liposome, either via diffusion through the thin aqueous tear film or via direct partitioning from the membrane of the vesicle to the membrane of the cell, was proposed as a possible pathway. 

The rotational microwave spectrum of a diatomic molecule has absorption lines (expressed as reciprocal wavenumbers cm ) at 20, 40, 60, 80 and 100 cm . Calculate the rotational partition function at 100 K from its fundamental definition, using kT/h= 69.5 cm" at 100 K. 

Absorption of trichloroethylene in humans is very rapid upon inhalation exposure. Trichloroethylene has a blood/gas partition coefficient that is comparable to some other anesthetic gases (i.e., chloroform, diethylether, and methoxyfluorene), but it is much more lipophilic than these gases. As a consequence of these properties, the initial rate of uptake of inhaled trichloroethylene in humans is quite high, with the rate leveling off after a few hours of exposure (Fernandez et al. 1977). The absorbed dose is proportional to the inhaled trichloroethylene concentration, duration of exposure, and alveolar ventilation rate at a given inhaled air concentration (Astrand and Ovrum 1976). Several studies indicate that 37-64% of inhaled trichloroethylene is taken up from the lungs (Astrand and Ovrum 1976 Bartonicek 1962 Monster et al. 1976). 

Octanol-water partition (log P) and distribution (log D) coefficients are widely used to make estimates for membrane penetration and permeability, including gastrointestinal absorption [77, 78], BBB crossing [60, 69] and correlations to pharmacokinetic properties [1]. The two major components of lipophilicity are molecular size and H-bonding [57], which each have been discussed above (see Sections 2.5 and 2.6). 

AM columns are another means of measuring lipophilic characteristics of drug candidates and other chemicals [99-103]. 1AM columns may better mimic membrane interactions than the isotropic octanol-water or other solvent-solvent partitioning system. These chromatographic indices appear to be a significant predictor of passive absorption through the rat intestine [128]. 

Liposomes, which are lipid bilayer vesicles prepared from mixtures of lipids, also provide a useful tool for studying passive permeability of molecules through lipid. This system has, for example, been used to demonstrate the passive nature of the absorption mechanism of monocarboxylic acids [131]. Liposome partitioning of... 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

B. W. Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption. Pharm. Res. 1999, 16, 882-888. 

Absorption, the Henderson-Hasselbalch Equation and the pH-partition Hypothesis... 

The following physico-chemical properties of the analyte(s) are important in method development considerations vapor pressure, ultraviolet (UV) absorption spectrum, solubility in water and in solvents, dissociation constant(s), n-octanol/water partition coefficient, stability vs hydrolysis and possible thermal, photo- or chemical degradation. These valuable data enable the analytical chemist to develop the most promising analytical approach, drawing from the literature and from his or her experience with related analytical problems, as exemplified below. Gas chromatography (GC) methods, for example, require a measurable vapor pressure and a certain thermal stability as the analytes move as vaporized molecules within the mobile phase. On the other hand, compounds that have a high vapor pressure will require careful extract concentration by evaporation of volatile solvents. 

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