Method Goals

Analytical method goals are often defined as method acceptance criteria for peak resolution, precision, specificity, and sensitivity. For instance, pharmaceutical methods for potency assays of an active pharmaceutical ingredient (API) typically require the following resolution 1.5 from the closest eluting components precision of retention time and peak area, 1-2% RSD and linearity in the range of 50-150% of the label claim. Other desirable characteristics include  

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After defining method goals, the next step is to gather sample and analyte(s) information such as those listed in Table 8.1. This information is useful for the selection of appropriate sample preparation procedures as well as the initial detection and chromatographic modes. If critical data are not available (e.g., pKa, solubility), separate studies should be initiated as soon as possible. 

Guidelines on mobile phase selection are discussed in Chapter 2, Section 2.3 and are illustrated in the case study below. After evaluation of the first sample chromatograms, further method development to fine-tune the separation will be performed until all method goals are achieved. Other bonded phases or column configurations can be selected to enhance method performance. These are discussed in the Section 8.6. 

Three method development cases studies of pharmaceuticals are used to illustrate the logical sequence in fine-tuning conditions to meet method goals. These are ... 

The above bi-objective optimization problem can be transformed into a SOO problem by the -constraint method via making OFj as an additional constraint. Besides this method, goal programming and the weighted-sum method can also be used to convert the MOO problem into a SOO problem. Interested readers are referred to Chapter 4 for more details... 

In the following sections, we will discuss the MCMP methods—goal programming, cempromise programming, and interactive methods, as examples of categories 1,2, and 3 type approaches. 

Gather Sample Information and Define Method Goals... 

Different types of methods have different goals. The method goals are usually defined as specificity, accuracy, precision, sensitivity, and robustness, or more specifically as resolution, linearity, recovery, repeatability, and quantitation limit for an assay and impurity method. The method goal for an identification test is often defined as specificity. This chapter mainly focuses on the assay and impurity method. 

In addition, method goals also change with the phase of each project. For an early-phase project, robustness and ruggedness are not required for an API method. However, for a late-phase project, robustness and ruggedness are required for an API method. The comparison of method goals between early- and late-phase projects is made in Table 1.1. 

Table 1.1 Comparison of API Method Goals Between Early- and Late-Phase Projects...

After carefully selecting separation conditions and optimizing the method, the method must be validated. However, if any parameter cannot meet the predefined method goals, the method must be re-optimized or even redeveloped. 

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