Intermediates study

While only the most elementary mechanistic studies have been undertaken, their results indicate that it is the excited singlet which is the reactive species in some instances, while the triplet undergoes reaction in others. To data, there has been little detailed information derived from experiments which would allow one to establish mechanisms or to discuss the lifetimes and energies of the occurring intermediates. Studies have been restricted in large measure to product determination. 

Lu, C. Lin, W. Wang, W. Han, Z. Yao, S. Lin, N. (2000). Riboflavin-(VB2) photosensitized oxidation of 2 -deoxyguanosine-5 -mono-phosphate (dGMP) in aqueous solution A transient intermediates study. Physical Chemistry Chemical Physics, Vol.2, 0anuary 2000), pp.329-334, ISSN 1463-9076. 

Germain, Comte de Saint-. Intermediate studies in alchemy alchemical formulas for self-mastery., 1982. 182p. 

Cationic complexes are key intermediates in a great variety of organic transformations such as isomerizations, rearrangements, addition reactions, aromatic substitutions, polymerization and others. Long-lived cationic complexes are important structural models for these intermediates. Studies of such complexes by modem physical methods provide valuable insight regarding their structure and reactivity. 

Formal Stability Studies — Long-term and accelerated (and intermediate) studies undertaken on primary or commitment batches according to a prescribed stability protocol to establish or confirm the retest period of a drug substance or the shelf life of a drug product. Impermeable Containers — Containers that provide a permanent barrier to the passage of gases or solvents (e.g., sealed aluminum tubes for semisolids, sealed glass ampoules for solutions). 

A detailed kinetic and product (intermediate) study (Y. Ogata, A. Kawaqsaki, F. Sugiura, Tetrahedron 1968, 24, 5001) describes the rapid decomposition of HMTA ... 

Identification of glycosyl-enzyme intermediates. Studies with pure enzymes often make it possible to confirm directly the existence of enzyme-bound intermediates. The intermediates detected are frequently glycosyl esters of glutamate or aspartate side chain... 

Lomoth R, Naumov S, BredeO (1999) Transients in the oxidation of pyrimidines with SO4 " structure and reactivity of the resulting radicals. J PhysChem A 103 6571-6579 Lu C, Lin W, Wang W, Flan Z, Yao S, Lin N (2000) Riboflavin(VB2) photosensitized oxidation of 2 -deoxyguanosine-5 -monophosphate (dGMP) in aqueous solution a transient intermediates study. Phys Chem Chem Phys 2 329-334... 

The FDA Draft Stability Guidance, which predates the ICH Draft Revised Guidance, sdoes not provide testing frequency for intermediate studies or accelerated studies for API. It indicated a minimum of four test stations (e.g., 0,2,4, and 6 months) for accelerated studies for drug products. 

The high relative humidity conditions cited in Table 4 apply to APIs and solid dosage forms. Low relative humidity conditions should be used for liquid drug products in semipermeable container-closure systems. The ICH Draft Revised Stability Guidance suggests low RH conditions of 40%+ 5% relative humidity for long-term studies, 60%+ 5% relative humidity for intermediate studies, and not more than 25% RH accelerated studies. 

Accelerated studies are carried out for 6 months, intermediate studies for 12 months and long-term studies for the duration of the proposed retest period for APIs and expiration dating period for drug products. 

However, in most cases a combination of kinetic and spectroscopic methods can resolve such uncertainties to a large extent. The third method is based on the study of model compounds. Model compounds are fully characterized metal complexes that are assumed to approximate the actual catalytic intermediates. Studies on the reactions of such compounds can yield valuable information about the real intermediates and the catalytic cycle. With the advent of computational speed and methods, quantum-mechanical and other theoretical calculations are also increasingly used to check whether theoretical predictions match with experimental data. 

Reactions of hydrated electrons with organic compounds, 7, 115 Reactions in dimethyl sulphoxide, physical organic chemistry of, 14, 133 Reactive intermediates, study of, by electrochemical methods, 19, 131 Reactivity indices in conjugated molecules, 4, 73... 

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