Resources analytical techniques

In this chapter, pharmaceutical and health-care products, such as prescription drugs, generic drugs, OTC products, animal health products, dietary supplements (vitamins and herbal drugs), and biotechnology-derived products, are discussed in relationship to the format of preformulation reports. Topics of the preformulation study are discussed in detail. Models for some of the reports are provided in the hope that the pharmaceutical development team will devise an individual report format based on particular needs and resources. Analytical techniques useful for preformulation and regulatory conformity or requirements relative to product registration processes are also enumerated. 

Some of these areas involve actions that primarily you, the ultimate user, must take (e.g., carefully defining written objectives for the QRA project team). Other areas involve decisions that you will influence, but that should be left to the team s discretion (e.g., selection of specific analytical techniques). Still other areas will require your careful interaction and negotiation with the QRA team to ensure that their final product meets your needs (e.g., defining analysis scope and available resources). 

The development of a quantitative method involving LC-MS is, in principle, no different from developing a quantitative method nsing any other analytical technique the intensity of signal from the analyte(s) of interest in the unknown sample is compared with that from known amounts of the analyte. The task of the analyst is to decide how this is best achieved knowing the resources available and the purpose for which the results are required. 

Drop all methodologies that impose impractical demands on human and capital resources many analytical techniques, while perfectly sound, will he eliminated at this stage because manpower, instrumentation, and/or scheduling requirements make them noncompetitive. 

Increased computational resources allow the widespread application of fundamental kinetic models. Relumped single-event microkinetics constitute a subtle methodology matching present day s analytical techniques with the computational resources. The singleevent kinetic parameters are feedstock invariant. Current efforts are aimed at mapping catal) t properties such as acidity and shape selectivity. The use of fundamental kinetic models increases the reliability of extrapolations from laboratory or pilot plant data to industrial reactor simulation. 

Single-event microkinetics describe the hydrocarbon conversion at molecular level. Present day analytical techniques do not allow an identification of industrial feedstocks in such detail. In addition current computational resources are not sufficient to perform simulations at molecular level for industrial feedstock conversion. These issues are addressed using the relumping methodology. 

Hidy, G. M. Characterization of Aerosols in California (ACHEX). Vol 2. Experimental Methods Analytical Techniques. Final Report. (Prepared for California Air Resources Board) Thousand Oaks, Calif. Rockwell International, 1974. 

In summary, in a critical assessment of an economic analysis, careful attention should be paid to the choice of analytical technique, the relevance of the comparator and the identification, measurement and valuation of resources, ensuring that the latter components are relevant to the stated viewpoint of the analysis. Published checklists are useful tools that aid in the assessment of these analyses. 

Partly because of this concern, the Wisconsin Department of Natural Resources, in cooperation with the Electric Power Research Institute, initiated an extensive study of Hg cycling in seepage lakes of north-central Wisconsin (14). The mercury in temperate lakes (MTL) study used clean sampling and subnanogram analytical techniques for trace metals (10, 17) to quantify Hg in various lake compartments (gaseous phase, dissolved lake water, seston, sediment, and biota) and to estimate major Hg fluxes (atmospheric inputs, volatilization, incorporation into seston, sedimentation, and sediment release) in seven seepage lake systems. 

Research by Burton and Price (38) demonstrated that Ba/Sr ratios generated by ICP emission spectroscopy (ICP-ES) can be used to infer the diet (marine verses terrestrial) of prehistoric populations. In this experiment we duplicate results obtained by Burton and Price for the Paloma samples. Our results show that the Ba/Sr ratios obtained by LA-ICP-MS are comparable in precision and accuracy to ICP-ES data (Figure 12). Although it is not unexpected that a coastal population would rely heavily upon marine resources, there are applications where this type of research would have value. What we have done here is demonstrate the efficacy of LA-ICP-MS to this line of research by demonstrating that it is possible to generate results similar to those obtained by other analytical techniques. 

In order to take maximum advantage of available resources, the parallel approach should be applied to all aspects of the analytical approach. If a highly parallel analytical technique is added to a sequential reactor system, or vice versa, the total throughput of the system may not increase at all. Just as a chain is only as strong as its weakest link, the high-throughput setup is only as fast as its slowest component. 

The ideal high-throughput analytical technique would be efficient in terms of required resources and would be scalable to accommodate an arbitrarily large number of samples. In addition, this scalability would be such that the dependence of the cost of the equipment to perform the experiments would scale in a less than linear manner as a function of the number of samples that could be studied. The only way to accomplish this is to have one or more aspects of the experimental setup utilize an array-based approach. Array detectors are massively multiplexed versions of single-element detectors composed of a rectangular grid of small detectors. The most commonly encountered examples are CCD cameras, which are used to acquire ultraviolet, visible and near-infrared (IR) photons in a parallel manner. Other examples include IR focal plane arrays (FPAs) for the collection of IR photons and channel electron multipliers for the collection of electrons. 

One of the most important problems in oceanography and water resources science is the effect of the concentrations and concentration changes of trace metal ions on the nature of the water system (1-6). Recently, there has been much interest in the apparent increased concentration of metal ions such as mercury, lead, and iron. This concern is, at best, speculative since there are insuflBcient analytical techniques to establish baseline normal concentrations with the precision expected of good analytical methods. For example, there has been tremendous publicity concerning the level of mercury concentrations in edible fish in Lake St. Clair (7, 8, 9). Even in extreme cases, there was considerable disagreement in the true mercury concentrations in the fish analyzed. Rottschafer, Jones, and Mark (9) conducted a comparative study in which a homogenous sample of Coho salmon flesh was dis-... 

There is also a maturation of the analytical techniques investors can use to integrate sustainability considerations into their established investment practices. While there are many possible alternatives, the work of the World Resources Institute on a technique built around conventional tools of financial analysis is quite promising (Repetto and Austin, 2000 Austin and Sauer, 2002 Austin et al., 2003). 

Following the introduction presented in Chapter 1, this book discusses the application and use of specific analytical techniques (mass, infrared, and nuclear magnetic resonance spectrometry, chromatography, and capillary electrophoresis) in the combinatorial chemistry field (Chapters 2-6). It also discusses how to make sense of the vast amounts of data generated (Chapter 7), details how the actual libraries of compounds produced are utilized (Chapter 8), and lists some of the vast commercial resources available to researchers in the field of combinatorial chemistry (Chapter 9). 

The underlying premise of pharmacoeconomic analyses is that fiscal resources are scarce and that there is a need to make decisions based on the relative value of different interventions in creating better health and/or longer life. There are five main analytical techniques used to evaluate the incremental value of products. These are cost-consequence analysis (CCA) cost-effectiveness analysis (CEA) cost-benefit analysis (CBA) cost-minimisation analysis (CMA) and cost-utility analysis (CUA). Although the identification and valuation of the cost component (numerator) of these analyses are similar, it is the identification and valuation of the consequences (denominator) that truly differentiate these analytic techniques. A brief description of each of these techniques follows. 

The LT system was mobilized to the site after preparation of a detailed site specific Work Plan and Health and Safety Plan. An Air Permit was received from the Stanislaus County Air Resources Board. The soil was excavated from a 50 ft. by 50 ft. area. During treatment the treated soil was composited daily and analyzed using a Hanby Environmental Test Kit for petrolevim hydrocarbons. This simple test kit, which provides rapid soil analysis, was used as a means of process control. The processed soil operating temperature and retention time was optimized at 422°F and 22 minutes, respectively. The treated soil samples were collected and analyzed for TPH and BTEX s by an independent third party. The average of the 18 samples collected and analyzed using approved analytical techniques are provided on Table I. The treated soil exceeded the treatment criteria of 100 ppm total petrolevim hydrocarbons and 700 ppb toluene. 

---