Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1991-12-13
pubmed:abstractText
The new drug RG 12561 (I) is a lactone that is undergoing clinical evaluation for its cholesterol lowering effect based on potent HMG CoA reductase inhibitory activity displayed by its open hydroxy acid form. To determine the dispositional characteristics of the drug, a method was developed for determination of the two forms in plasma. A 0.25-ml aliquot of plasma was deproteinized with 0.5 ml of methanol, and the lactone was extracted with hexane-ethyl acetate (75:25, v/v). The methanolic plasma was then acidified followed by extraction of the hydroxy acid with hexane-ethyl acetate. The extracts were dried, reconstituted and analyzed by isocratic, reversed-phase high-performance liquid chromatography using ultraviolet absorbance at 254 nm. The separations were performed utilizing a C18 column with mobile phase consisting of acetonitrile, 2-propanol and 0.1 M acetate buffer (pH 5), the proportions of which differed depending on the form of drug analyzed. The method was found to be selective and a quantitation limit of 50 ng/ml was established. Validation studies demonstrated that the method was sufficiently accurate and precise for determining disposition of the drug in the dog.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9673
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
567
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
491-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Method for separation and determination of lactone and hydroxy acid forms of a new HMG CoA reductase inhibitor (RG 12561) in plasma.
pubmed:affiliation
Preclinical Drug Disposition Department, Rhone-Poulenc Rorer Central Research, Horsham, PA 19044.
pubmed:publicationType
Journal Article