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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-8-16
pubmed:abstractText
Spectroscopic and chromatographic methods (HPLC, HPLC-MS, NMR) were used to observe, separate and identify products of radiolysis of thiamphenicol (TF), irradiated in the solid state at room temperature and atmospheric pressure with an electron beam from a linear accelerator to doses between 25 and 800 kGy. Nine products of radiolysis of thiamphenicol were identified, among them were TF amine, dichloroacetic acid, 4-methylsulfonylbenzoic acid, demono- and dedichloroderivative of TF, 2,2-dichloro-N-{3-hydroxy-1-[4-(methylsulfonyl)phenyl]-1-oxopropan-2-yl}acetamide and 3-({1,3-dihydroxy-1-[4-(methylsulfonyl)phenyl]propan-2-yl}amino)-3-oxopropanoic acid. The process of radiodegradation of TF was proposed as consisting of several parallel primary reactions (dehalogenation, oxidation of the OH group at C(1), hydrolysis of the amide bond, a rapture of the C(2)-C(3) bond of propan-1-ol) and secondary reactions (carboxylation and oxidation). The use of high doses, well above the sterilization dose of 25 kGy, allowed observation of changes of TF content as a function of radiation dose, calculation of radiolytic yield (G(-TF)) and kinetic parameters of the degradation reaction. It was found that the standard sterilizing dose lowers the content of TF by only 0.1% and the radiolytic efficacy of the process of radiodegradation is 0.76 molecules/100eV. Further increase in the dose lowers the content of TF to 92.1% for 800 kGy dose and leads to an increase in the value of G(-TF). It was also found that the summative process of radiodegradation of TF exposed to a beam of electrons of 10 kGy/s follows the first order reaction kinetics with a degradation constant of k=0.001s(-1). On the basis of the experiments conducted it can be stated that the radiolysis of TF in the presence of an E-beam, in substantia, follows multidirectional course in the same way as radiolysis of chloramphenicol. TF exposed to the standard sterilizing dose of 25 kGy degrades only by 0.1%, the amount acceptable by the ICH, and forms only one product of radiolysis (TF amine) and therefore we conclude that it can be sterilized by ionizing radiation under the conditions described above.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-264X
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
826-32
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Identification of radiolysis products of solid thiamphenicol.
pubmed:affiliation
Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Grunwaldzka, Pozna?, Poland. bmarcin@ump.edu.pl
pubmed:publicationType
Journal Article