Determination of the novel hydroxymethyl glutaryl coenzyme A reductase inhibitor (RP 61969) and its dihydroxy acid hydrolysis product in human plasma by reversed-phase high-performance liquid chromatography
Page, K.M.; Mallett, C.D.; Page, M.R.
Journal of Chromatography 575(2): 319-324
1992
ISSN/ISBN: 0021-9673 PMID: 1629313 Document Number: 403760
A method is described for the determination of the novel hydroxymethyl glutaryl coenzyme A reductase inhibitor RP 61969(I) and its hydrolysis product, the dihydroxy acid RP 62420(II), in human plasma. A structural isomer of I is used as internal standard. Both I and II were extracted from acidified plasma with diethyl ether. The dried residues were reconstituted in the high-performance liquid chromatography mobile phase and chromatographed on a 5 .mu.m ODS2 column. The mobile phase used was aqueous dipotassium phosphate + tera-n-butyl ammonium bromide (both 10 mM)-acetonitrile-methanol (60:40:5, v/v). At a flow-rate of 1.5 ml min-1 and ambient temperature, the retention time of II is 3.5 min, that of the internal standard is 5 min, and that of I is 8 min. The method has been validated and applied to the assay of plasma samples resulting from cell-plasma distribution experiment in human whole blood.