Impurity profile comparison

Figure 4.8. Comparison of impurity profiles for the same chemical intermediate from two different suppliers. The impurity peak-areas for each chromatogram were tallied in 0.02 area-% bins for each vendor, the data was normalized by dividing by the number of chromatograms. Vendor A s material has many more peaks in the 0.05-0.2% range, which drives the total impurity level to =5.2% (vs. 1.9 for Vendor B) for <0.2% the number of excess peaks above 0.2% does not appear as dramatic, but greatly adds to the total impurity level = 13.3 v.v. = 2.3% ...

Impurity profiles for new batches, comparison to previous (Ames) batch(es)... 

Impurity profiles for new batches and comparison to previous toxicology batches... 

The testament to the success of LC/NMR is the burgeoning number of publications in the area. Impurity profiling, as has been pointed out in a recent review of the area [148], has been relatively lightly reported, with only some relatively early industrial examples [132, 133], which used home-built interfaces and a field strength of 400MHz, through a comparison of LC/NMR with other methods... 

As noted in Section 4.2.4.2, NMR may be particularly useful for impurity profiling because of the simplicity of the fluorine spectrum. Mistry etal. showed that fluorine-containing impurities in bulk dmg could be detected and quantitated down to approximately 0.1 mole% (by comparison with HPLC-UV traces) [205]. 

Stromberg L, Lundberg L, Neumann H, Bobon B, Huizer H, and Van der Stelt NW (2000) Heroin impurity profiling. A harmonization study for retrospective comparisons. Forensic Science International 114 67-88. 

Source Stromberg, L., et al. "Heroin Impurity Profiling A Harmonization Study for Retrospective Comparisons." Forensic Science International 114 (2000), 67-88. 

Wienen E, Deuhner R, Holzgrahe U. Composition and impurity profile of multisourse hulkware of gentamicin - a comparison. Pharmeuropa 2003 15 273-279. 

CE is applied to two major categories of quality release testing identity and impurity testing. Identification assays are intended to ensure the unique identity of an analyte in the sample. This is normally achieved by comparison of a property of the sample (e.g., spectrum, chromatographic behavior, chemical reactivity, etc.) to that of a reference standard. As shown in Figure 9, CZE can be used to determine identity for monoclonal antibodies and proteins based on their unique electrophoretic profile. 

Figure 9. The radial concentration profiles for the impurities detected in two adjacent breakdown trees 5A-1 and 5A-2. Note the breaks in the logarithmic concentration scale and also the essentially constant concentration of sulphur in comparison with the large variations in the Na, Cl, K and Ca concentrations.

There are also a number of new analytical techniques available for the comparison of samples. Traditionally, drugs are compared on the basis of their impurity content. Little attention, until recently, had been applied to the use of DNA profiling for drug identification and comparison - such an approach offer great... 

Diffusion of impurity atoms in bulk substrate under the porous layer is fairly different from diffusion of the same species in nonporous crystals. Figure 2.16 shows boron atom profiles in bulk substrate under the porous layer (formed at the same conditions) after diffusion at different temperatures. Coordinate x = 0 corresponds to the interface porous layer-bulk substrate. The diffusion profile of boron atoms in nonporous SiC substrate after diffusion at the same conditions (2000 °C, 10 min) is also presented in this plot for comparison. It is seen that the maximum concentration of boron atoms diffused from the porous layer into bulk... 

Many manufacturers already possess the data necessary to prepare a validation of the process and thus demonstrate that it works consistently. For example, limitations of a reaction and/or purification step are usually identified in the development phase. Known impurities and tests to be used to determine their levels are also established at this phase. Thus, when the process is scaled up to production lot/batch sizes, a comparison can be made with development lot/batches. Scale up and development reports, along with purity profiles, would constitute an appropriate validation report... 

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