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.
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 microns ODS2 column. The mobile phase used was aqueous dipotassium phosphate +tetra-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 a cell-plasma distribution experiment in human whole blood.
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Dagenham Research Centre, Rhône Poulenc Rorer Ltd., Essex, UK.
Mallett
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D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D006868:Hydrolysis; D006880:Hydroxy Acids / Q000097:blood*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007546:Isoquinolines / Q000097:blood*; D011714:Pyrans / Q000097:blood*
D006880:Hydroxy Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007546:Isoquinolines; D011714:Pyrans; C075612:RP 61969; C075613:RP 62420