Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2005-9-26
pubmed:abstractText
The naturally occurring alkaloid (-)-sophocarpine (SC) has been developed as a novel anti-coxsackieviral agent for potential treatment of viral myocarditis. However, there is currently no rapid, sensitive method available for ascertaining systemic exposure during the course of SC toxicity studies. The development and full validation of the first rapid and sensitive method, based on liquid chromatography with tandem mass spectrometry (LC/MS/MS), for determination of SC in plasma is reported here. This new assay increases sample throughput by using minimal sample clean-up procedures and short chromatographic analysis times. The bio-matrix effect on the ionization of SC and the internal standard, (-)-stepholidine, was investigated for method development and validation, and two organic solvents (methyl tert-butyl ether and ethyl acetate) were found for sample preparation that led to low matrix effects. The new analytical method was used to analyze plasma samples obtained from a repeated-dose toxicity study of SC in beagle dogs. The results of the toxicokinetic analysis indicated that the systemic exposure to SC was proportional to the dose, and that no significant accumulation of SC was observed after 3 months of repeated treatments with intravenous SC at 7.5, 15, or 30 mg/kg/day. This sensitive and specific LC/MS/MS technique can form the basis for accurate quantification of SC in various biological fluids for preclinical and clinical pharmacokinetic evaluation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0951-4198
pubmed:author
pubmed:copyrightInfo
2005 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2840-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A new method for measurement of (-)-sophocarpine, a candidate therapeutic for viral myocarditis, in plasma: application to a toxicokinetic study in beagle dogs.
pubmed:affiliation
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies