Separation methods generic

Providing economic and fast generic separation methods that can be applied with confidence in development and control laboratories to a large number of samples of variable composition to provide important information in short time to synthetic chemists, either for fast sample screening, or for generating impurity profiles... 

In terms of organization, the text has two main parts. The first six chapters constitute generic background material applicable to a wide range of separation methods. This part includes the theoretical foundations of separations, which are rooted in transport, flow, and equilibrium phenomena. It incorporates concepts that are broadly relevant to separations diffusion, capillary and packed bed flow, viscous phenomena, Gaussian zone formation, random walk processes, criteria of band broadening and resolution, steady-state zones, the statistics of overlapping peaks, two-dimensional separations, and so on. 

Despite the broad-based utility of separation methods, a priori prediction of operating conditions for the separation of a given API and its impurities has remained elusive. However, systematic approaches, or the use of generic conditions, can be exploited in method development. This chapter has endeavoured to summarize these approaches within the context of the goals that a method should achieve in the various stages of pharmaceutical development. 

Mutton, LM. Fast Generic HPLC Methods, pp.73-85 in Valko, K., ed.. Separation Methods in Drug Synthesis and Purification, Elsevier Science, Amsterdam, (2000). 

The latter method is a generic one for a wide range of capillary viscometers. A separate method directed to a specific commercial high-pressure capillary viscometer is currently under development in ASTM Committee D.02, Subcommittee 7. 

The first step is to establish a suitable analytical method to quantify the analyte. This is usually done by RP-HPLC with a C8 or C18 column. In some cases this step can be quite labor intensive, especially when none of the generic separation methods available in the laboratory is suitable for the substance of interest. 

The information required to obtain a base-case process flow diagram is discussed and categorized into the six basic elements of the generic block flow process diagrana. The need to obtain reaction kinetics, thermodynamic data, and alternative separation methods is discussed in the context of building a base-case process. Special enphasis is placed on alternative distillation schemes and the sequencing of columns needed for such separations. 

Combining the What-If and Checklist analysis methods uses their positive features while compensating for their separate shortcomings, For example, a checklist is hascti on generic process experience and may i.i c incomplete insights into the design,... 

A method for the development of a generic LC-electrospray-MS method for the analysis of acidic compounds using experimental design has been reported [5], From an HPLC perspective, this type of analysis often requires the use of an ion-pairing reagent to obtain separation however, many of these, such as tetraalkylammonium ions, are involatile and have undesirable effects on the performance of the mass spectrometer and more volatile alternatives have to be found - in this case, triethylamine was used. 

Other, similar methods for measuring surface-surface interactions, which come under the generic heading of surface force apparatus, include the crossed-filament method. This utilizes a beam deflection technique similar to that now being used in some AFMs for the measurement of surface displacement [94]. Another technique for displacement measurement used in a similar SFA is that of a capacitance transducer. Both techniques suffer the criticism that separation is not measured at the point of interest, i.e., the gap between the two surfaces as measured in the FECO technique. 

In most situations analysts can achieve a rapid reasonable separation of compounds using an appropriate standard CE method with generic operating conditions [877]. This eliminates or reduces dramatically the need for method development. Major instrumental error sources in CE are detection, integration and injection. General guidelines for validation of CE methods are available and similar to those of HPLC [878]. Validated CE methods often perform the same as, or better than, the corresponding HPLC methods. 

Chiral method development is often referred to as one of the most difficult fields in terms of development time. Interaction with a chiral selector is required to achieve separation but the enantioselectivity of a given selector for a given chiral molecule is a priori unknown. For some compounds, it can take several days to find suitable separation conditions when using sequential approaches. Therefore, industry most often defines generic separation strategies, which are often kept internally or are... 

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