Forced degradation studies of rapamycin: identification of autoxidation products.
Summary of "Forced degradation studies of rapamycin: identification of autoxidation products."
The immunosuppressant drug rapamycin, also known as Sirolimus, underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds, which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products, epoxides and ketones, were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time. Observed rapamycin isomers were also addressed. Computational chemistry was used to provide mechanistic insights. Formation of the majority of the rapamycin products could be rationalized with free radical-mediated autoxidation reactions involving alkene and alcohol sites. Methodological aspects of oxidative stress testing are discussed.
Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, USA. firstname.lastname@example.org
This article was published in the following journal.
Name: Journal of pharmaceutical and biomedical analysis
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22088479
- DOI: http://dx.doi.org/10.1016/j.jpba.2011.10.017
Medical and Biotech [MESH] Definitions
Forced Expiratory Volume
Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity.
Forced Expiratory Flow Rates
The rate of airflow measured during a FORCED VITAL CAPACITY determination.
Tor Serine-threonine Kinases
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Indinavir sulphate was subjected to forced degradation under hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH guidelines. It was degraded under aci...
Abacavir sulphate was subjected to forced degradation under the conditions of hydrolysis (acid, alkali and neutral), oxidation, photolysis and thermal stress as prescribed by ICH. Eight degradation pr...
LC-MS/TOF, LC-MS(n), on-line H/D exchange and LC-NMR studies on rosuvastatin degradation and in silico determination of toxicity of its degradation products: a comprehensive approach during drug development.
The present study dealt with the forced degradation behaviour of rosuvastatin under ICH prescribed stress conditions. The drug was found to be labile under acid hydrolytic and photolytic conditions, w...
The present study was designed to characterize the possible degradation products of toremifene under varied conditions as prescribed by ICH guidelines Q1A(R2). The forced degradation studies were cond...
The purpose of this work was to study the mechanistic pathways of degradation of polysorbates (PS) 20 and PS80 in parenteral formulations. The fate of PS in typical protein formulations was monitored...
The purpose of this study is to evaluate whether adding estradiol to rapamycin better prevents coronary artery reblockage after drug-eluting stent implantation.
This is a research study designed to look at the biological effects of two drugs on leukemia cells. In this study, we are comparing the effects of drugs called corticosteroids when used a...
The goal of this study is to determine the rapamycin dose equivalent to the recommended phase II/III dose of temsirolimus and determine the observed toxicities and anti-tumor response of r...
The purpose of this study is to evaluate the efficacy of 3 different rapamycin-eluting-stent platforms to reduce coronary artery reblockage after stent implantation
The purpose of this study was to determine if rapamycin reduced angiomyolipomata volume in patients with tuberous sclerosis complex or lam.