Determination of falintolol, a new aliphatic beta-adrenergic antagonist, in whole blood by gas chromatography with electron-capture detection: geometric isomers resolution

Falintolol oxalate, a new beta-adrenergic antagonist, is characterized by the presence of an oxime function and exists in a racemic form as a mixture of syn- and anti- isomers in a ratio of about 8:2. This article describes a selective gas chromatographic method for the resolution of the geometric isomers and the quantitation of the drug. The unchanged falintolol and internal standard, a related compound, are separated from blood by a solvent extraction under alkaline conditions, and then the drug is derivatized. The heptafluorobutyric derivatives are chromatographed on an SE-30 capillary quartz column and detected with a nickel-63 electron-capture detector. Because the syn- and anti- isomers of falintolol display comparable chromatographic responses, the sum of the two geometrical isomers is used for the quantitation of falintolol in blood. This method allows small serial blood samples in conscious rats, and 0.05 microgram of falintolol/0.1 mL of blood can be routinely determined. A calibration curve is prepared for the blood extracts. Linearity is observed in the study range (0.05 to 1 microgram/0.1 mL of blood). No interference by endogenous substances is observed. The procedure is applied successfully to drug absorption in rats when repeated oral doses are administered.