Linked Life Data

9300914

Source:http://linkedlifedata.com/resource/pubmed/id/9300914

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-14
pubmed:abstractText
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 ligh 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1387-2273
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
696
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-115
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Profiling degradants of paclitaxel using liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry substructural techniques.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA.
pubmed:publicationType
Journal Article