Composite assay validation results

Table 9.9. Validation Results of a Composite Assay Method (Assay and Impurity) of a Drug Substance...

Table 9.9 shows a summary of validation results for the composite test method for a drug substance shown in Figure 9.9. The development process of this particular method is described in Chapter 8, Section 8.8.2. The key analytes of this assay are the API, an impurity eluting (impurity 1) at 6.4min that has been identified as an isomer of the API and the immediate synthetic precursor eluting at 7.6min. 

It must be pointed out that the atomic absorption system as used today, cannot accurately determine the calcium level of a solution. The reason for this is that results will vary depending upon the other elements present and the composition of the solution. Since it is impossible to duplicate every feature of the particular serum being analyzed, results have to be compared to standards which have been made up in serum dialysates. Such standards are available in the form of the Versatols where the calcium has been dialyzed out and then weighed back. This is distinct from substances such as Validate, which are used as controls and which values are re-sults of analysis. The variability of serum composition has significantly widened what is now considered the "normal range" for serum Ca assay when done by atomic absorption (37a). 

The method yielded >99% label claim of the API for the composite tablet assay. Table 3 lists the results of a filter validation study showing the quantitative recovery of the API from most membrane media. 

Surface Potential. Shah and Schulman have proposed that interaction between dipoles of uncharged lipids in mixed monolayers should result in a change in surface potential, AV. Linearity of the relation of AV to composition of the lecithin-cholesterol monolayer was taken to indicate absence of interaction (17). We do not agree with Shah and Schulman, since surface potential does not appear to be a valid criterion for assaying interaction between dipoles of uncharged lipids. Except for the speculations of Shah and Schulman (17, 18), there is neither theoretical nor experimental evidence that dipole-dipole interactions have... 

The procedure we used in earlier sections to build and validate the crude unit model relies on the availability of crude assays and associated density curves. While this procedure can provide very accurate results, it can be challenging to implement directly. Often, the composition of the crude entering the atmospheric unit is ill-defined and only product yield and operating measiuements are available. How do we construct a model using this limited amount of information. ... 

---