Direct high-performance liquid chromatographic determination of (R)- and (S)-propranolol in rat microdialysate using on-line column switching procedures

Two different column-switching HPLC systems (CSWs), employing restricted ac cess material for initial pretreatment of biological samples, were develope d for the determination of propranolol enantiomers in microdialysate. CSW 1 was a single-pump set-up based on an initial sample clean-up step with a R P-18 ADS precolumn coupled with an ovomucoid analytical column for direct d rug enantioseparation. For the two-pump column set-up (CSW 2), a teicoplani n analytical column was applied for the enantioselective assay after initia l sample pretreatment using a RP-8 ADS precolumn. The inter-day precision o f the CSW 1 ranged from 0.5 to 5.1% for (R)-propranolol and from 5.1 to 10. 5% for (S)-propranolol, The limit of detection (LOD) was set at 10 ng/ml an d 15 ng/ml for (R)- and (S)-propranolol, respectively. Inter-day relative s tandard deviation values of the CSW 2 ranged from 1.1 to 9.9% for (R)-propr anolol and from 1.3 to 9.6% for (S)-propranolol. The LOD of the method was 3.0 ng/ml for (R)-propranolol and 2.5 ng/ml for (S)-propranolol. Both appro aches were successfully applied for stereoselective monitoring of unbound p ropranolol levels in rat microdialysates. (C) 2000 Elsevier Science B.V. Al l rights reserved.