Impurities/degradants isolation

FIGURE I Impurity/degradant isolation and Identification process flowchart (RRT relative retention time PRI = process-related impurity). 

FIGURE 2 Impurity/degradant isolation and identification process flowchart. 

FIGURE 9 Impurity/degradant isolation and identification process flow chart. PRI, process-related impurity STD. standard RRT, relative retention time MW, molecular weight. 

Ahuja S, Aisante KM, eds. Handbook of Isolation and Characterization of Impurities in Pharmaceuticals. Vol. 5. Separation Science and Technology Alsante KM, Hatajik TD, Lohr LL, Santafianos D, Sharp TR. Solving Impurity/Degradation Problems Case Studies. Chapter 14. San Diego, CA Academic Press 2003 361-400. 

The process of characterization of impurities described in this chapter uses a designed approach for the isolation of unknown impurities and degradants in pharmaceutical drug substances. This approach focuses on efficiency, so that the success of data collection is maximized. The isolation of pure material is crucial when trying to identify the structure of an unknown impurity/degradant. Once the unknown has been isolated, it can be submitted for structure elucidation using mass spectrometry and NMR spectroscopy. 

Chapter 14 provides practical guidance with case studies on isolating and characterizing process-related impurities and degradation products for pharmaceutical drug candidates. The case studies utilize isolation or synthesis in conjunction with mass spectral and NMR characterizations. A collaborative multiple disciplinary strategy has been found to be the most efficient way to solve impurity/degradation product problems. 

G. Pharma D3 Degradation Database ISOLATION OF IMPURITIES/DEGRADANTS... 

The quaHty, ie, level of impurities, of the fats and oils used in the manufacture of soap is important in the production of commercial products. Fats and oils are isolated from various animal and vegetable sources and contain different intrinsic impurities. These impurities may include hydrolysis products of the triglyceride, eg, fatty acid and mono/diglycerides proteinaceous materials and particulate dirt, eg, bone meal and various vitamins, pigments, phosphatides, and sterols, ie, cholesterol and tocopherol as weU as less descript odor and color bodies. These impurities affect the physical properties such as odor and color of the fats and oils and can cause additional degradation of the fats and oils upon storage. For commercial soaps, it is desirable to keep these impurities at the absolute minimum for both storage stabiHty and finished product quaHty considerations. 

In 1933, R. Kuhn and his co-workers first isolated riboflavin from eggs in a pure, crystalline state (1), named it ovoflavin, and deterrnined its function as a vitamin (2). At the same time, impure crystalline preparations of riboflavin were isolated from whey and named lyochrome and, later, lactoflavin. Soon thereafter, P. Karrer and his co-workers isolated riboflavin from a wide variety of animal organs and vegetable sources and named it hepatoflavin (3). Ovoflavin from egg, lactoflavin from milk, and hepatoflavin from Hver were aU. subsequently identified as riboflavin. The discovery of the yeUow en2yme by Warburg and Christian in 1932 and their description of lumiflavin (4), a photochemical degradation product of riboflavin, were of great use for the elucidation of the chemical stmcture of riboflavin by Kuhn and his co-workers (5). The stmcture was confirmed in 1935 by the synthesis by Karrer and his co-workers (6), and Kuhn and his co-workers (7). 

The objectives of the soil persistence experiments were (1) to learn the effect of soil type and concentration on the TCDD degradation rate, (2) to isolate and characterize degradation products from DCDD and TCDD, and (3) to determine whether chlorodioxins could be formed from chlorophenol condensation in the soil environment. This last study was essential since quality control at the manufacturing level could reduce or eliminate the formed dioxin impurity. But the biosynthesis of chlorodioxins by chlorophenol condensation in the soil environment could not be controlled and would have connotations for all chlorophenol-de-rived pesticides if formation did occur. The same question needed to be answered for photochemical condensation reactions leading to chloro-... 

One trial formulation, stored at 60° for 7 months showed degradation.74 xhe one impurity that was isolated and identified (with the aid of mass spectrometry) is dihydrotriamcinolone acetonide (Figure 1), an intermediate in the synthesis of halcinonide. This compound also possesses topical antiinflammatory activity.69... 

---