Method development considerations during

During method development, considerable work may be required to make a judicious choice for the lower limit of quantification (LLOQ). To obtain an initial... 

For many applications, surface properties, such as hardness, coupled with high chemical inertia are required. Non-oxide ceramics have the required characteristics, but their sintering necessitates temperatures that are often incompatible with the thermal stability of the support to be protected. Methods for synthesizing these materials in the form of depositions or coatings have been developed considerably during the last few decades [WEI 92]. They can be divided into two groups ... 

Development of efficient and reliable HPLC methods for dissolution testing can at times be problematic. Several factors need to be taken into consideration during method development. 

The following considerations, when applied during method development, are likely to produce more robust, reliable, and transferable methods (a) the concerns of the customer (user) are considered in advance, (b) key process input variables are identified, (c) criticaTto-quality factors are determined, (d) several method verification tests are installed, (e) proactive evaluation of method performance during development is performed, (f) continuous customer involvement and focus are institutionalized, and (g) method capability assessment (suitability to be applied for release testing against specification limits) is established. 

This is of considerable importance given the throughput demands placed on HTS groups in modern pharmaceutical companies. However, the method has been streamlined considerably during its development and, furthermore, is amenable to automation. 

The first actinide metals to be prepared were those of the three members of the actinide series present in nature in macro amounts, namely, thorium (Th), protactinium (Pa), and uranium (U). Until the discovery of neptunium (Np) and plutonium (Pu) and the subsequent manufacture of milligram amounts of these metals during the hectic World War II years (i.e., the early 1940s), no other actinide element was known. The demand for Pu metal for military purposes resulted in rapid development of preparative methods and considerable study of the chemical and physical properties of the other actinide metals in order to obtain basic knowledge of these unusual metallic elements. 

During the past few years great efforts have been made to overcome the 50% threshold of enzyme-catalyzed KRs. Among the methods developed, deracemization processes have attracted considerable attention. Deracemizations are processes during which a racemate is converted into a non-racemic product in 100% theoretical yield without intermediate separation of materials [5]. This chapter aims to provide a summary of chemoenzymatic dynamic kinetic resolutions (DKRs) and chemoenzymatic cyclic deracemizations. 

The motivation behind the considerable effort that was exerted in the development of DCV [42, 49, 50, 69] was based on the need to make CV and LSV quantitative tools for the study of electrode kinetics. At that time, there were three major problems that had to be overcome. These were (a) the precision in the measurement of Ep and AEp, (b) the problem with accurately defining the baseline for the reverse sweep and (c) the problem as to how to handle Rn in a practical manner. The development of DCV did indeed provide suitable solutions to all three of these problems, although the methods developed to handle the Ru problem [41, 42] only involve the derivative of the response in terms of precision necessary for the measurements. More recent work [55, 57] is indicative that the precision in Ep/2, Ep) and AEP measurements can be as high as that observed during DCV (see Sect. 3.4). Also, a recent study in which rate constants were evaluated using CV, DCV, and double potential step chronoamperometry for a particular electrode reaction showed that the precision to be expected frcm the three techniques are comparable when the CV baseline, after subtracting out the charging... 

The ultimate in selectivity in HPLC detection is seen with the use of mass-spectrometric detection, and for many applications this could be seen as the ideal detection method. However, more mundane considerations such as size of the instrumentation and limited budgets combine to reduce HPLC-MS to a relatively small number of applications which most effectively exploit its unique properties. When such practical constraints are taken into account, the real detector coimected to the HPLC system usually turns out to be a device that is a compromise, and its performance characteristics need to be taken into account during the development of many analyses just as much as the performance of the column or any other component of the HPLC system. For example, lack of detection selectivity may require extra method development to completely resolve an interfering peak, or lack of sensitivity could force the inclusion of an extraction-concentration step in an analytical method to achieve detectable levels of analyte. 

The most common variables affecting Heckel analysis are the rate and duration of compression, the degree of lubrication, and even the size and shape of the dies and punches (86) hence these variables should be taken into consideration during analysis. Although the use of the Heckel relationship to study the compression behavior of pharmaceutical powders/granules has been criticized (81), it still remains one of the most commonly used methods in the field of formulation research and development of pharmaceutical solids. 

The step-by-step approach recommended in the ISO Guide and the top down approach have been seen as alternative and substantially different ways of evaluating uncertainty, but the comparison between method development protocols and ISO approach above shows that they are more similar than appears at first sight. In particular, both require a careful consideration and study of the main effects on the result to obtain robust results accounting properly for each contribution to overall uncertainty. However, the top down approach relies on that study being carried out during method development to make use of the data in ISO GUM estimations, the detailed data from the study must be available. 

---