Determination of 2-n-octadecylindole-5-carboxylic acid in human plasma by high-performance liquid chromatography.
A method is described for the determination of the novel hypocholesterolaemic drug, 2-n-octadecylindole-5-carboxylic acid (I) in plasma. A homologue of I is used as the internal standard. Methanol is added to the plasma sample in order to precipitate the plasma proteins, followed by centrifugation and removal of the supernatant. This is reduced to dryness by heating under oxygen-free nitrogen, prior to reconstitution in the chromatographic mobile phase. The solution is assayed by injection on to a 5 micron particle size ODS2 analytical column, protected by a disposable RP-18 packed guard column, using an isocratic mobile phase of acetonitrile-water-isopropyl alcohol-formic acid (75:275:150:2.5, v/v). Detection is by ultraviolet absorbance at 276 nm. At a flow-rate of 1.5 ml min-1 and ambient temperature, the retention time of the drug is 16 min, whilst that for the internal standard is 21 min. This method has been validated and successfully used to assay clinical trial plasma samples. Basic pharmacokinetic parameters are presented.
Jones
G D
GD
Biopharmaceutical Research Department, Dagenham Research Centre, Rhône-Poulenc Ltd., Essex, U.K.
Evans
C D
CD
Facchini
V
V
Lewellen
O R
OR
D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D000960:Hypolipidemic Agents / Q000097:blood*; D007211:Indoles / Q000097:blood*; D008297:Male; D013056:Spectrophotometry, Ultraviolet
D000960:Hypolipidemic Agents; D007211:Indoles; C063254:2-n-octadecylindole-5-carboxylic acid