Shelf-life of mobile phases

The updates and improvements of this new edition are mainly to be found in details such as new references and technical descriptions which match today s instrumentation. Four new sections have been written, namely on the shelf-life of mobile phases, the mixing cross, the phase systems in ion chromatography, and on measurement uncertainty. Some equations in the zeroth chapter . Important and Useful Equations for HPLC, have new numeric values because a porosity of 0.65 is more realistic than 0.8 for chemically bonded phases. 

It is a good practice to prepare only as much mobile phase as will be used within short time. The shelf life of aqueous solutions without an organic solvent is very limited if rigorous quality standards need to be followed. ... 

Key elements of a validation should be documented by raw data, for example, robustness, with respect to pH of the mobile phase, the mobile phase composition, the shelf life of reference samples, and the column temperature. 

Unstable compounds are problematic. A sample purified in the laboratory might have a short shelf-life and poor performance as a standard. Compounds altered by assays are also inconvenient. For example, substituted benzylic alcohols can dehydrate under acidic HPLC conditions, or carboxylic esters can hydrolyze in aqueous mobile phase. An impurity isolated from an active pharmaceutical ingredient as an organic salt of an organic compound poses two problems at once. The analyst must account for both the acid and the base. In the case of a toluenesulfonic acid salt of an aliphatic amine, two different methods of detection might be needed. The toluenesulfonic acid in a reverse-phase HPLC assay can by monitored by UV light, but the aliphatic amine, with no chromophore, must be measured by a different technique. 

The various crystal modifications of a substance will possess different melting points and thereby have different solubilities (Brittain, 2002). Only one solid phase is thermodynamically stable for a given set of environmental conditions. The most stable form has the lowest free energy and therefore the lowest solubility. Metastable forms can theoretically be used to improve solubility, but the kinetics of the transformation back to the stable crystal modification must then be taken into account. In suspension, solvent-mediated transition is generally too rapid to give a product with an acceptable shelf-life. In solid dosage forms, it may be possible, however, to utilize a less stable crystal modification. Due to the decreased molecular mobility in the solid state the transition rate can be low. 

Most solvents are stable but some, like tetrahydrofuran (THF), have a very short shelf life. This should be noted at the time of preparation and an expiry date assigned to the mobile phase that does not exceed the expiry date for the THF. UV cut-off levels for some commonly used solvents are given in Table 3.2. 

The influence of temperature on the reaction rate follows the Arrhenius equation (cf. 2.5.4). Thus by studying a reaction and measuring the rate constants at two or three high temperatures, one could then extrapolate with a straight line to a lower temperature and predict the rate of the reaction at the desired lower temperature. However, these data allow only a prediction of the shelf life when the physical and chemical properties of the components of a food do not alter with temperature. For example, as temperature rises a solid fat goes into a liquid state. The reactants may be mobile in the liquid fat and not in the solid phase. Thus, shelf life will be underestimated for the lower temperature. 

It is difficult to speculate on the importance of something which has not yet been imequivo-cally measured in food polymers, but clearly if material was encapsulated in an amorphous matrix with different properties from the more usual mobile phase, then ageing and plas-ticisation could be significantly different, having both positive and deleterious effects on shelf life. Similarly, a substantial fraction of rigid material could affect the permeability to reactants, such as oxygen. 

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