Profiling degradants of paclitaxel using liquid chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry substructural techniques

• Published in: Journal of chromatography. B, Biomedical sciences and applications Biomedical sciences and applications, 1997-08, Vol.696 (1), p.99-115
• Main Authors: Volk, Kevin J, Hill, Susan E, H. Kerns, Edward, Lee, Mike S
• Format: Article
• Language: English
• Subjects: Analysis; Antineoplastic Agents, Phytogenic - analysis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Biological and medical sciences; Carbonates - chemistry; Chromatography, High Pressure Liquid - methods; General pharmacology; Hydrochloric Acid - chemistry; Hydrogen Peroxide - chemistry; Light; Mass Spectrometry - methods; Medical sciences; Oxidants - chemistry; Paclitaxel; Paclitaxel - analysis; Paclitaxel - chemistry; Paclitaxel - metabolism; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet
• ISSN: 0378-4347; 1387-2273
• DOI: 10.1016/S0378-4347(97)00208-9

A rapid and systematic strategy based on liquid chromatography–mass spectrometry (LC–MS) profiling and liquid chromatography–tandem mass spectrometry (LC–MS–MS) substructural techniques was utilized to elucidate the degradation products of paclitaxel, the active ingredient in Taxol. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray MS, and MS–MS to rapidly and accurately elucidate structures of impurities and degradants. In these studies, degradants induced by acid, base, peroxide, and light were profiled using LC–MS and LC–MS–MS methodologies resulting in an LC–MS degradant database which includes information on molecular structures, chromatographic behavior, molecular mass, and MS–MS substructural information. The stressing conditions which may cause drug degradation are utilized to validate the analytical monitoring methods and serve as predictive tools for future formulation and packaging studies. Degradation products formed upon exposure to basic conditions included baccatin III, paclitaxel sidechain methyl ester, 10-deacetylpaclitaxel, and 7-epipaclitaxel. Degradation products formed upon exposure to acidic conditions included 10-deacetylpaclitaxel and the oxetane ring opened product. Treatment with hydrogen peroxide produced only 10-deacetylpaclitaxel. Exposure to high intensity light produced a number of degradants. The most abundant photodegradant of paclitaxel corresponded to an isomer which contains a C3–C11 bridge. These methodologies are applicable at any stage of the drug product cycle from discovery through development. This library of paclitaxel degradants provides a foundation for future development work regarding product monitoring, as well as use as a diagnostic tool for new degradation products.