Degradation analysis case study

A bulk lot sample of drug substance contained an unknown process-related impurity at 0.4% in case study B.7. To meet project time lines, it was necessary to identify the impurity. Mass spectral data indicated that the impurity had a molecular weight of M+12 (compared to the parent). LC/MS/ MS data indicated that the change was located in the sugar portion of the molecule. Isolation and NMR analysis was required to provide more structural information on the impurity. This again was a process-related impurity not observed in forced degradation studies therefore, effort was placed on finding an enriched mother liquor sample. 

The development of the model of the degradation process is based on the identification of the IPs influencing the degradation of the component. In the present case study, this has been done by resorting to a FMECA analysis performed by safely analysis. The identified IPs are the following ... 

On the other hand, GC, because of the physical separation it effects, furnishes both a qualitative and a quantitative analysis of polymer-plasticiser mixtures with almost the same ease as the analysis of plasticisers alone, and this is discussed further in Chapter 5.1. It suffices to submit the sample, prepared as for the pyrolysis of plastics, to a controlled pyrolysis in order to disengage the vaporised plasticisers. The polymer is partially degraded, but its pyrolysis products were in all the cases studied by Guiochon and Hennicker [82] much lighter than the plasticisers and in no way prevented their separation and identification. Figure 4.18 shows the separation obtained of four plasticisers (a) dibutyl succinate, (b) tributyl phosphate, (c) dimethyl sebacate and (d) diethyl phthalate and the pyrolysis products of polyvinyl chloride. The latter are eluted during the first minute of operation. 

The presented case study on inter-Cu ET in 4xNiR demonstrates the experimental challenges associated with PCET reactions. The existence of multiple pathways renders any mathematical analysis rather complex, especially if only one macroscopic parameter - as in this case EXobs is experimentally accessible. All attempts to employ the pH indicator phenol red in the laser experiments to obtain rate constants of the PT steps (kpxobs) failed, which we attribute to potential photo-reduction and/or photo-degradation processes of the dye. Due to... 

The remainder of this article is organized as follows. Section 2 presents the proposed degradation model for systems with degradation dependency. Monte Carlo simulation procedures to solve the model are presented in Section 3. Section 4 presents one case study on one subsystem of a residual heat removal system (Coudray Mattel 1984) from Electricite de France (EDF). Numerical results and analysis are presented in Section 5. Section 6 concludes the work. 

Rong Pan, Taeho Crispin, 2011. A Hierarchical Modeling Approach to Accelerated Degradation Testing Data Analysis A Case Study. Quality and Reliability Engineering International, 27(2) 229-237. 

CP-944,629 is a substituted l,2,4-triazolo[4,3-a]pyridine. This compound was designed as a selective inhibitor of the stress-activated kinase p38a, and was nominated as potential disease-modifying drug for rheumatoid arthritis (RA). Purposeful degradation experiments performed on this compound was analyzed by RP-HPLC with UV detection. Analysis of the solid-state photostability samples indicated a lack of mass balance with an assay value of 25% impurities totaling 18% by total area percent. Closer inspection of the sample revealed imdissolved material in the bottom of the volumetric flask. This case study focuses on the identification of the degradation product that resulted in the undissolved material and source of the lack of mass balance. 

Thermal volatilisation analysis (TVA) and sub-ambient thermal volatilisation analysis (SATVA) techniques are described. In addition to rate profiling of the volatile product flux of thermal degradation under high-vacuum conditions through measurement of pressure in the vacuum line as a function of sample temperature, the TVA technique is shown to afford a convenient method for an on the basis of volatility under high-vacuum conditions, of product fractions of thermal degradation for subsequent spectroscopic analysis. The capacity and flexibility of TVA as a platform for these analyses are illustrated in a case study format by degrading poly(bisphenol A, 2-... 

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