Chiral separation of beta-blockers by high-performance liquid chromatography and determination of bisoprolol enantiomers in surface waters

Abstract

Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due to their high consumption and incomplete degradation in waste water, they may reach surface waters and affect aquatic organisms. To address this issue we developed a chromatographic method suitable for determining beta-blocker enantiomers in surface waters. It was tested on five beta-blockers (acebutolol, atenolol, bisoprolol, labetalol and metoprolol) and validated on bisoprolol enantiomers. Good enantioseparation of all analysed beta-blockers was achieved on the Chirobiotic V column with the mobile phase composed of methanol/acetic acid/triethylamine (100/0.20/0.15 v/v/v) at a flow rate of 0.5 mL/min and column temperature of 45 °C. Method proved to be linear in the concentration range from 0.075 µg/mL to 5 µg/mL, and showed good recovery. The limits of bisoprolol enantiomer detection were 0.025 µg/mL and 0.026 µg/mL and of quantification 0.075 µg/mL and 0.075 µg/mL. Despite its limitations, it seems to be a promising method for bisoprolol enantiomer analysis in surface water samples. Further research could focus on waste water analysis, where enantiomer concentrations may be high. Furthermore, transferring the method to a more sensitive one such as liquid chromatography coupled with tandem mass spectrometry and using ammonium acetate as the mobile phase additive instead of acetic acid and triethylamine would perhaps yield much lower limits of detection and quantification.

Chemoenzymatic Synthesis of Chiral Building Blocks Based on the Kinetic Resolution of Glycerol‐Derived Cyclic Carbonates

“…For example, (S)-propanol and (S)-atenolol are more potent than the corresponding (R)enantiomers. [53,54] To evaluate the feasibility of this approach for the preparation of (S)-TAGEs, the obtained product (S)-1 a (er = 94 : 6) was used as starting material with different phenols as nucleophiles under basic conditions. The reaction was carried out with NaOH in ethanol by modification of a protocol reported by Egri et al for 3-chloropropane-1,2-diol.…”

Progress in the Enantioseparation of β-Blockers by Chromatographic Methods

“…Plenty of researchers [ 15 , 74 , 75 , 76 , 77 ] chose commercial chirobiotic columns, including teicoplanin containing Chirobiotic T and T2, teicoplanin aglycone containing Chirobiotic TAG, ristocetin A containing Chirobiotic R, and vancomycin containing Chirobiotic V and V2, as their chiral selector for the enantioseparation of β-blockers.…”

“…In the case of β-blockers, the cardiac β-blocking activity generally resides in their S (-) enantiomer [ 11 , 12 , 13 ], and the reported S : R activity ratio ranges from 33 to 530 [ 14 ] due to the diverse degree of binding affinity to the β-receptor. For example, S -propranolol is 100 times more potent than R -propranolol [ 15 ]. Therefore, the separation of racemates of β-blockers is essential both in the laboratory and industry.…”

Analytical research on the separation and residue of chiral pesticide triadimenol in fruit and vegetable puree

“…Currently, GC [6,7], GC-MS [8,9], CEC [10,11], HPLC [12,13], LC-MS/MS [14,15], and other methods play an important role in the separation of chiral compound. Dong et al [3,5] and Wang et al [16] have reported that triadimenol stereoisomers were successfully separated on Chiral column using HPLC method.…”