Monitoring of ajmaline in plasma with high-performance liquid chromatography

A rapid, reliable and sensitive assay for routine determination of ajmaline in plasma by high-performance liquid chromatography with fluorimetric detection is presented. A low limit of detection in plasma (less than 1 ng/ml ajmaline) could be achieved by the extraction of plasma samples and the use of fluorimetric detection. Deproteinization of the plasma sample instead of extraction, or the use of an ultraviolet detector, yielded a higher limit of detection (less than 50 ng/ml). Two different eluents were studied. Eluent 1 allowed clear separation of ajmaline from isoajmaline and sandwicine, but did not separate isoajamaline from sandwicine. With eluent 2, separation of isoajmaline and sandwicine was achieved, but separation of ajmaline from sandwicine was less optimal than with eluent 1. Therefore, eluent 1 was used for further clinical studies. No interference was observed from therapeutic doses of other commonly co-administered drugs, such as acetylsalicylic acid, digoxin, digitoxin, ranitidine, dopamine, dobutamine, furosemide, captopril or glycerol trinitrate. In addition, the chemical stability of ajmaline and a possible rearrangement of ajmaline to its stereoisomers isoajmaline and sandwicine was studied in vivo and in vitro. Ajmaline proved to be unusually stable under both in vivo and in vitro conditions.