| An impurity present in some samples of SIN-1 oxidizes it to nitric oxide in anaerobic solutions. | |
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MedLine Citation:
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PMID: 8160198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Morpholino-N-nitrosoaminoacetonitrile (SIN-1), a nitrovasodilator metabolite of the drug, molsidomine, is widely used in studies on the pharmacology and toxicology of nitric oxide (NO) because solutions of SIN-1 'spontaneously' release NO in a pathway involving molecular oxygen. Preliminary results, however, suggested that SIN-1 could react with hemoglobin in anaerobic solutions to release NO and form NO-hemoglobin. Electron paramagnetic resonance (EPR) studies showed that heme(III) of methemoglobin was not being reduced, thereby not serving as the oxidant in the reaction generating NO-hemoglobin. When anaerobic solutions of SIN-1 and hemoglobin kept in the light and in the dark were compared, substantially more NO-hemoglobin was eventually generated in the dark, indicating that SIN-1 did not undergo photochemical decomposition to NO under the conditions used. Solutions of NO-hemoglobin were equally stable under these same conditions of light and dark. The initial pH (7.0) of stirred, unbuffered solutions of SIN-1 decreased at nearly the same rate whether or not oxygen was present. Anaerobic and aerobic solutions plateaued at the same pH, namely 5.4. Anaerobic solutions of SIN-1 in phosphate buffer, pH 7.4, released NO to the gas phase, where it was identified by trapping it with hemoglobin on agarose beads and deriving the characteristic NO-hemoglobin EPR spectrum. High pressure liquid chromatography revealed the presence of an unknown species with a retention time between that of SIN-1 and molsidomine. Samples from two different lots of SIN-1 contained this impurity which appears to oxidize SIN-1 to products that release NO in the absence of oxygen. This unknown impurity may be unstable toward light. |
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Authors:
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Y Wang; L G Rochelle; H Kruszyna; R Kruszyna; R P Smith; D E Wilcox |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicology Volume: 88 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 1994 Mar |
Date Detail:
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Created Date: 1994-05-18 Completed Date: 1994-05-18 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: IRELAND |
Other Details:
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Languages: eng Pagination: 165-76 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755-3835. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anaerobiosis Animals Drug Contamination* Electron Spin Resonance Spectroscopy Hemoglobins / drug effects Humans Molsidomine / analogs & derivatives*, metabolism Nitric Oxide / metabolism*, toxicity Oxygen / pharmacology* Rabbits Solutions / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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HL 14127/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hemoglobins; 0/Solutions; 10102-43-9/Nitric Oxide; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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