Peak tracking

A well-known method for peak tracking is based on the phase-system switching idea, " which was developed to solve problems of mobile phase incompatibility in LC/MS target compound analysis. An analytical column is usually connected to a trapping column in tandem mode. A switching valve is placed after the UV detector, and the flow of nonvolatile eluents is directed through the trapping column to waste. When the peak of interest elutes from the analytical column it is... 

To identify all compounds of the drug-impurities mixture, the use of an orthogonal set of systems can be beneficial. The expected selectivity differences between these systems combined with MS detection and the use of peak tracking and matching algorithms should enhance the chance that all different compounds occurring in the mixture can be identified. 

Furthermore, in a pharmaceutical development environment (working to GMP), redeveloping a method is not a simple task since peak tracking (by LC-MS) and validation may be required and, in the case of registered methods, results obtained by modified methods may not be acceptable. In such cases, it may be more efficient to use a preparative approach followed by conventional tube NMR where optimum sensitivity can be obtained through the use of cryogenic probes (Figure 6.48) or low-volume 1 mm probes [90]. 

The method proceeds in three stages. The first stage involves estimation of the tonal components using a DFT magnitude-based peak tracking algorithm closely related to... 

For simple mixtures containing only a few components, prepare each solute at a different concentration. This in combination with diode-array UV detection simplifies peak tracking. For complex mixtures computerized experimental design speeds methods development [6],... 

The current second-generation tools offer more promise due to (a) a focus on secondary detection techniques for peak tracking and (b) better automation tools offered by instrument vendors. 

Peak Matching in Method Optimization. An initial solution to the problem of peak tracking across multiple experiments was the isolation of each impurity on a preparative or semiprep scale, followed by injection of each component individually. The chromatographic world has essentially rejected this concept outright. Very few chromatographers have the time or willingness to isolate standards for each component. The use of crude samples and mother... 

G. Xue, A. D. Bendick, R. Chen, and S. S. Sekulic, Automated peak tracking for comprehensive impurity profiling in orthogonal liquid chromatographic separation using mass spectrometric detection, / Chromatogr. A 1050 (2004), 159-171. 

Either isolated diastereomers or racemic mixtures are preferred for the KPSS. If no isolated samples are available, a sample that contains an enriched level of the diastereomers may be used, but peak tracking may be hampered as diastereomers are challenging to separate from the API. These molecules are subject to elution order changes. 

It may be necessary to include individual excipients and/or mixtures as part of the KPSS when analyte/excipient interferences occur. Preservatives and antioxidants are normally assayed for during release testing and stability evaluation of a formulation. Therefore, isolated samples of these excipients should be included in the KPSS in addition to the representative placebo or excipient soup samples to facilitate peak tracking. Inclusion of these samples is more critical for high-potency compounds, where the ratio of excipient to drug can be very large. 

FIGURE 3 Drug substance peak tracking example. 

Drug substance lots with different impurity profiles can be combined for peak-tracking purposes, provided the impurity profiles are relatively simple and that the abundance of each impurity in the final solution is sufficient to obtain accurate photodiode array UV data. 

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