An improved HPLC-fluorescence stereoselective method for analysis of (+)-S- and (-)-R-sotalol enantiomers in plasma...

A simplified high performance chromatographic method (HPLC) was performed for sotalol enantiomers in plasma samples for purposes of investigation of the kinetic disposition of racemic sotalol in cardiac arrhythmic patients under multiple dose and multidrug therapy regimens. After addition of NaCl:Na2CO3 (4:1) and plasma protein precipitation by acetonitrile:methanol mixture (1:1) the supernatant was evaporated. The residue containing sotalol racemate was submitted to derivatization reaction with (-)-menthylcloroformate to R(-)- and S(+)-sotalol diastereoisomers. The diastereoisomers were resolved in HPLC, by a C18 column with fluorescent detection under lexcitation = 235 nm and lemission = 310 nm. The retention times for R- and S-sotalol were 20 and 22 minutes while that of internal standard S(-)-atenolol, was 17 minutes. The detection limit for each enantiomer was 12.5 ng/mL and intra-day/inter-day coefficients of variation were less than 10% for each enantiomer within a concentration range of 200 and 2000 ng/mL. The method was appropriate for the objective proposed.