Analysis Methods during Drug Development

VALIDATION OF ANALYSIS METHODS DURING DRUG DEVELOPMENT 

The validation process begun in Phase I is extended during Phase II. In this phase, selectivity is investigated using various batches of drugs, available impurities, excipients, and samples from stability studies. Accuracy should be determined using at least three levels of concentration, and the intermediate precision and the quantitation limit should be tested. For quality assurance evaluation of the analysis results, control charts can be used, such as the Shewart-charts, the R-charts, or the Cusum-charts. In this phase, the analytical method is refined for routine use. 

In Phase III, the final dosage formulation has been established and the pivotal clinical trials are being conducted. Degradation products have been identified, so the method selectivity should be reevaluated to ensure that all degradants can be detected and quantitated. The analytical methods are completely validated, and appropriate for routine quality assurance and control purposes. The type and frequency of system suitable testing (SST) should be determined, and an excellent publication on SST for chromatography systems is available [47], 

In addition, for reporting a routine analytical result, the result should include its confidence interval CF [28], or with same meaning term, uncertainty C/ [29] or standard certainty STC [48]. The result should be reported as  

Analytical method validation, which must be performed by every regulated laboratory, deals with the testing of significant method characteristics to ensure that under 

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Validation of analysis methods during drug development... 

There are many HPLC methods that are developed during the process of drug development. The chromatographer needs to understand the aim of analysis in order to make judicious choices prior to the commencement of method development and the implications it may have on the final method that is developed. The following should be considered method development time, the maximum run time for analysis, the number of samples expected per week, the complexity of the mixture, the structure of the main analyte (physicochemical properties), possible degradation pathways (i.e., hydrolysis, oxidative, photolysis, dethydration, thermolytic, racemization), and whether the analyte or analytes are ionizable. 

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