Method development and optimisation

Personal computer systems are capable of running software to assist in selecting chromatography parameters such as column type, stationary 

COMPONENTS = UNRETD PEAK TIME AREA/HT REJECT 

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Although PFE lacks a proven total concept for in-polymer analysis, as in the case of closed-vessel MAE (though limited to polyolefins), a framework for method development and optimisation is now available which is expected to be an excellent guide for a wide variety of applications, including non-polyolefinic matrices. Already, reported results refer to HDPE, LDPE, LLDPE, PP, PA6, PA6.6, PET, PBT, PMMA, PS, PVC, ABS, styrene-butadiene rubbers, while others may be added, such as the determination of oil in EPDM, the quantification of the water-insoluble fraction in nylon, as well as the determination of the isotacticity of polypropylene and of heptane insolubles. Thus PFE seems to cover a much broader polymer matrix range than MAE and appears to be quite suitable for R D samples. 

If the focus is on a wide variety of additives in polyolefins only the OSM/TSM procedure of Marcato and Vianello [210] appears to be far reaching, despite the fact that this total design approach must have required considerable effort in terms of method development. On the other hand, in comparison considerably more method development and optimisation appears to be necessary for SFE of a single polymer/additive matrix, but even then still without the demonstrated benefit of a total approach [322]. Where analyte integrity is of greater concern recourse should be taken to less... 

METHOD DEVELOPMENT AND OPTIMISATION OE CONDITIONS IN ISOCRATIC HPLC... 

Chemometrics has been defined in some texts [155] as the entire process whereby data are transformed into information used for decision-making. It is this definition that is the most applicable to separation sciences, more specifically in method development and optimisation in liquid chromatography. In this example, chemometrics has been used to predict optimum separation conditions based on empirical data and other separation information. Chemometric approaches to method development can be based on either sequential simplex models [156] or simultaneous fixed factorial designs [157] or interactive mixture designs [158] which combine the advantages of simultaneous and simplex models. 

But in order to compare different GCxGC sets and conditions, for both method development and optimisation, a quantitative measure of orthogonality is necessary. Several methods have been proposed to quantitatively determine orthogonality and are discussed in the next section. 

In-polymer Additive Analysis Method Development and Optimisation.732... 

A typical example of HPLC method development and validation was provided by Boneschans et al. [9]. They developed an HPLC method for piroxicam benzoate and its major hydrolytic degradation products, piroxicam and benzoic acid. The authors utilised a robust stationary phase (Phenomenex Luna, Cig), with an optimised mobile phase comprising of acetonitrile/water/acetic acid (45/7/8 v/v), and a flow rate of 1.5 ml/min. The operating pH of the mobile phase (pH 2.45) was selected on the basis that it is ca. 2 pH units from the pKa of the drug, and hence reasonably insensitive to changes in mobile-phase preparation. The injection volume was 20 pi with a detection wavelength of 254 nm. They utihsed... 

Two open-vessel wet digestion methods using mixtures of nitric and sulfuric acids and H2O2 were developed and optimised to determine metals in plants... 

Several methods have been developed over the years for the thermochemical characterisation of compounds and reactions, and the assessment of thermal safety, e.g. differential scanning calorimetry (DSC) and differential thermal analysis (DTA), as well as reaction calorimetry. Of these, reaction calorimetry is the most directly applicable to reaction characterisation and, as the heat-flow rate during a chemical reaction is proportional to the rate of conversion, it represents a differential kinetic analysis technique. Consequently, calorimetry is uniquely able to provide kinetics as well as thermodynamics information to be exploited in mechanism studies as well as process development and optimisation [21]. 

Altria KD, McLean R. Development and optimisation of a generic micellar electrokinetic capillary chromatography method to support analysis of a wide range of pharmaceuticals and excipients. J Pharm Biomed Anal 1998 18 807-813. 

King, B.W. Computer Aided Optimisation for Methods Development And Validation. Phase Separations, Deeside, Clwyd, 1993. 

This system is ideal for automatic method development and gradient optimisation. 

Danaher, M. O Keeffe, M. Glennon, J.D. Development and optimisation of a method for the extraction of benzimidazoles from animal liver using supercritical carbon dioxide, Anal.Chim.Acta, 2003, 483, 313-324. [albendazole fenbendazole mebendazole thiabendazole oxibendazole flubendazole oxfendazole netobimin triclabendazole cambendazole]... 

It is fair to say that advances in seismic surveys over the last decade have changed the way fields are developed and managed. From being a predominantly exploration focused tool, seismic has progressed to become one of the most cost effective methods for optimising field production. In many cases, seismic has allowed operators to extend the life of mature fields by several years. 

A key element in the development process is to select and optimise the most appropriate method for the delivery of the drug. Drugs may be administered by ... 

Published evidence highlights the efficacy of SFE. However, the method is highly matrix and analyte dependent and must be optimised for each combination of material and analyte. Interaction between analyte and matrix is often difficult to predict and optimisation of the extraction procedure is not simple. Understanding of the processes that occur during SFE has lagged behind instrumental developments. The results obtained from SFE are highly dependent on the operational parameters used during the extraction (Table 3.19). 

The task of embarking on method development for a new polymer/additive sample can be intimidating due to the number of parameters that can be varied during an extraction. Because cook-book methods are unavailable for most analyte-matrix pairs, analysts may feel they are condemned to use a trial-and-error approach to optimise extraction-collection conditions for SFE. However, a flow sheet considering the most important parameters in the SFE process is available [3]. There are several approaches to... 

The actual SFE extraction rate is determined by the slowest of these three steps. Identification of the ratedetermining step is an important aspect in method development for SFE. The extraction kinetics in SFE may be understood by changing the extraction flow-rate. Such experiments provide valuable information about the nature of the limiting step in extraction, namely thermodynamics (i.e. the distribution of the analytes between the SCF and the sample matrix at equilibrium), or kinetics (i.e. the time required to approach that equilibrium). A general strategy for optimising experimental parameters in SFE of polymeric materials is shown in Figure 3.10. 

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