acenocoumarol and acetonitrile

The aim of this work is to determine generic screening conditions and an initial simple separation strategy allowing the rapid separation of drug enantiomers in polar organic solvent chromatography (POSC). Four cellulose/amylose-based stationary phases were investigated in detail using two mobile phase basis solvents commonly applied in this mode, i.e. acetonitrile and methanol. Polar mode is interesting for use in purification of enantiomers. In a first step, the parameters potentially influencing the separation, such as addition of an alcohol to the polar organic solvent or the type of mobile phase additive(s), were examined by means of experimental designs. Afterwards, the factors found most important are investigated in more detail. Results showed that the cellulose- and amylose-based stationary phases have very broad and complementary enantiorecognition abilities in the POSC mode. The type of organic solvent for the mobile phase appeared to have a dramatic influence on the quality of the separation. Based on the results, a screening strategy was proposed. Enantioseparation was observed in more than 85% of the tested compounds and analysis times of last eluted peak were usually below 10 min.

Topics: Acenocoumarol; Acetonitriles; Alcohols; Chromatography, High Pressure Liquid; Metoprolol; Pharmaceutical Preparations; Polysaccharides; Stereoisomerism

Acenocoumarin and its acetamido metabolite, after extraction at pH 4.4, were analysed by isocratic reversed-phase high-performance liquid chromatography using aqueous acetonitrile (pH 4.90) as eluent. Warfarin was used as internal standard. The amino metabolite, after back-extraction into 0.5 N HCl, was derivatized by diazotization and heat treatment. The resulting product was analysed by the same reversed-phase system. The sensitivity of the method for acenocoumarin and its amino metabolite was in the range of 20 ng/ml. To achieve this sensitivity for the analysis of the acetamido compound, the acetonitrile content of the eluent had to be lowered. The assay was applied to the analysis of plasma samples of patients under acenocoumarin therapy. The disposition of the amino compound in rats was investigated.

Topics: Acenocoumarol; Acetonitriles; Animals; Body Fluids; Chromatography, High Pressure Liquid; Humans; Hydrogen-Ion Concentration; Rats; Warfarin