Enantioselective determination of sotalol enantiomers in biological fluids using high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic (HPLC) method for the determination of (+)-(S)-sotalol and (-)-(R)-sotalol in biological fluids was established. Following extraction with isopropyl alcohol from biological samples on a Sep-Pak C18 cartridge, the eluent was derivatized with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The diastereoisomeric derivates were resolved by HPLC with UV detection at 225 nm. Calibration was linear from 0.022 to 4.41 micrograms/ml in human plasma and from 0.22 to 88.2 micrograms/ml in human urine for both (+)-(S)- and (-)-(R)-sotalol. The lower limit of determination was 0.022 microgram/ml for plasma and 0.22 microgram/ml for urine. The within-day and day-to-day coefficients of variation were less than 7.5% for each enantiomer at 0.09 and 1.8 microgram/ml in plasma and at 0.44 and 4.4 micrograms/ml in urine. The method is also applicable to other biological specimens such as rat, mouse and rabbit plasma.