Pharmaceutical impurity identification: A case study using a multidisciplinary approach
| Autor: | Qicai Liu, Thomas R. Sharp, Andrew J. Jensen, Raggon Jeffrey W, Ronald Morris, Linda L. Lohr, Dinos Santafianos, Karen M. Alsante, Jeffrey W. Harwood, George L. Reid, Robert C. Friedmann, Wilcox Glenn Ernest, Peter Boutros, George J. Horan, Michel Couturier, John L. Tucker |
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| Rok vydání: | 2004 |
| Předmět: |
Active ingredient
Magnetic Resonance Spectroscopy Preparative hplc Computer science Sample (material) Analytical technique Analytical chemistry Pharmaceutical Science Characterization (materials science) Identification (information) Pharmaceutical Preparations Multidisciplinary approach Impurity Technology Pharmaceutical Biochemical engineering Drug Contamination |
| Zdroj: | Journal of Pharmaceutical Sciences. 93:2296-2309 |
| ISSN: | 0022-3549 |
| Popis: | A multidisciplinary team approach to identify pharmaceutical impurities is presented in this article. It includes a representative example of the methodology. The first step is to analyze the sample by LC-MS. If the structure of the unknown impurity cannot be conclusively determined by LC-MS, LC-NMR is employed. If the sample is unsuitable for LC-NMR, the impurity needs to be isolated for conventional NMR characterization. Although the technique of choice for isolation is preparative HPLC, enrichment is often necessary to improve preparative efficiency. One such technique is solid-phase extraction. For complete verification, synthesis may be necessary to compare spectroscopic characteristics to those observed in the original sample. Although not widely practiced, an effective means of getting valuable structural information is to conduct a degradation study on the purified impurity itself. This systematic strategy was successfully applied to the identification of an impurity in the active pharmaceutical ingredient 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulphonylurea. Identification required the use of all of the previously mentioned techniques. The instability of the impurity under acidic chromatographic conditions presented an additional challenge to purification and identification. However, we turned this acidic instability to an advantage, conducting a degradation study of the impurity, which provided extensive and useful information about its structure. The following discussion describes how the information gained from each analytical technique was brought together in a complementary fashion to elucidate a final structure. |
| Databáze: | OpenAIRE |
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