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Method development purposeful degradation

Forced degradation These testing studies are undertaken to degrade the sample deliberately. These studies, which may be undertaken in the development phase normally on the drug substances, are used to evaluate the overall photosensitivity of the material for method development purposes and/or degradation pathway elucidation. [Pg.422]

Analytical potency method development should be performed to the extent that it is sufficient for its intended purpose. It is important to understand and know the molecular structure of the analyte during the method development process, as this will facilitate the identification of potential degradation impurities. For example, an impurity of M + 16 in the mass spectrum of a sample may indicate the probability of a nitrogen oxide formation. Upon successful completion of method development, the potency method will then be validated to show proof that it is suitable for its intended purpose. Finally, the method validated will be transferred to the quality control laboratory in preparation for the launch of the drug substance or drug product. [Pg.11]

For the purpose of analyzing ezetimibe in combination with simvastatin, three HPTLC methods have been developed. The first method was developed by Shivshankar et al. [33] and yielded higher Rf values for either ezetimibe or simvastatin. In the method developed by Dhaneshwar et al. [30], a combination of toluene and isopropanol was shown to produce shorter Rf times for ezetimibe and simvastatin, leading to methods of shorter duration and lower mobile phase consumption. The recent method developed by Dixit et al. [31] used combination of acetone and n-hexane as the mobile phase and resulted in shorter Rf values when compared to the other two methods for assessing ezetimibe in combination with simvastatin. This method has also been validated to distinguish the degradation products of ezetimibe. Further, during the determination of ezetimibe in combination with atorvastatin, shorter Rf values were obtained as well as better peak shape when a combination of toluene and methanol was used as the mobile phase [30]. [Pg.121]

For a given API, there can be numerous ways to mix and match the available samples to construct the method development sample set. During early stages of development, only a few isolated intermediates and purposeful degradation samples may be available, making sample set selection relatively easy. Later in development, more isolated samples of the major degradants... [Pg.160]

If there are multiple salt forms or polymorphs being developed in parallel, it is helpful to perform comparative purposeful degradation studies on each form. Additionally, if there are stability issues with a particular salt form, it is advantageous to analyze the salt without drug substance as a control through the method development process as well as the free acid/base form of the com-... [Pg.98]

As emphasized in Section ILA, a proactive approach to HPLC method development should involve purposeful degradation at the early stages of development with the key degradation samples used in the method development process. See Figure 6 for an overview of the role of purposeful... [Pg.113]

FIGURE 6 Flow chart for the proactive role of purposeful degradation as an integral part of the method development process. [Pg.114]

FIGURE 8 Global perspective of the purposeful degradation, identification, and method development process. [Pg.116]

As previously discussed (Section 9.4.7b), extracted control matrix is used to assess the selectivity for the method under development. The selectivity of the method is a function of the sample preparation (extraction and clean-up), chromatography and mass spectrometry conditions that are used for the method. Assuming that the control matrix is representative of the sample matrix to be analyzed, and that method blanks have been used to demonstrate that the method is free of exogenous interferences due to solvents, or to containers or other apparatus (a source of interferences that is often overlooked in the method development process), an extracted blank is used to demonstrate that the method has sufficient selectivity for the intended analytical purpose. When interferences at the expected retention time of the analyte being quantified are detected, modifications to the sample preparation and chromatography (and sometimes the ions monitored hy the method) can be made to improve the selectivity of the method. Recall (Section 9.4.7b) that only re-analysis of incurred samples can reveal interferences resulting from metahoUtes or degradates of the analyte with either or both of the analyte and SIS. [Pg.513]


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See also in sourсe #XX -- [ Pg.116 ]




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