Propranolol enantioseparation

CEC was demonstrated in the analysis of /i-adrenergic antagonists using capillaries modified with propranolol-imprinted polymer. In situ molecular imprinting was performed via photo-polymerisation at — 20°C within a capillary that was premodified with 3-methacryloxypropyltrimethoxysilane. The time for UV irradiation was carefully determined so as to obtain a polymer coating of appropriate thickness. Enantioseparation of the racemate of propranolol was successfully demonstrated with a separation factor of 1.12 and a resolution factor of 1.26. 

Figure 4. Enantioseparations of propranolol in HPLC using capillary column (100 pm x 25 cm) packed with Chiralcel-OD material [120].

Three amino alcohols, propranolol, clenbuterol and cycloclen-buterol, could be enantioseparated on an achiral column by reversed phase HPLC (62). These alcohols are shown in Figure 1.24. 

It is obviously of interest to compare the same chiral selector in both aqueous and nonaqueous buffers from a mechanistic point of view (enantiomer migration order, intermolecular forces involved in complex formation and chiral recognition, structure of complexes, etc.). Enantioseparations of many chiral analytes have already been described with the same chiral selector in aqueous and nonaqueous buffers [66-70]. Only very recently the enantiomer migration order of chiral -blocker drug propranolol was studied in both aqueous and nonaqueous buffers. The enantiomer migration order was the same in the case of several CDs applicable... 

Fig. 21 LC and SFC enantioseparations of propranolol on a derivatized tyrosine Pi ride CSP. Mobile-phase conditions LC, 95 5 hexane/(ethanol containing 1% n-propylamine) (v/v) SFC, 90/10 carbon dioxide/(methanol containing 1% n-propylamine) (v/v) [179]. Molecular modeling results are presented for (a) optimized structure of (/J)-propranolol without CO2 and (b) optimized stiucture of (/J)-propranolol with CO2. The intramolecular hydrogen bonding is denoted by an arrow (adapted from [183])...

Fig. 2 The chromatograms of enantioseparation using (/ )-MA, iV-trimethyl-2-aminobutanol-bis(trifluoromethanesulfon)imidate CIL 5 as chiral selector, (a) propranolol in HPCE, 10 mmol/L CIL 5 voltage, 16 kV, with anodic detection at 254 nm (b) enantioseparation of 2,2 -diamino-l,r-binaphthalene in HPLC eluent H2O-CH3CN (6 4, v/v) containing 10 mmol/L of chiral selector 5, detection, 254 nm (c) enantioseparation of citronellain GC on 5, split ratio 80 1, FID. Adapted from [76]...

Yuan et al. found that the CIL, (/ )-fV,fV,fV-trimethyl-2-aminobutanol-bis (triflu-oromethanesulfonyl) imide (5), is an excellent chiral selector that could be used in CE for enatioseparation of various compounds (Fig. 2) [76]. For instance, this CIL afforded the enantioseparation of propranolol which is a commonly used beta blocker (Fig. 2A) [76]. 

In Reference 60, three dual systems were applied for the enantioseparation of duloxetine, cetirizine, citalopram, sulconazole, laudanosine, amlodipine, propranolol, atenolol, and nefopam. These three systems mix glycogen (a branched polysaccharide) with either chondroitin sulfate A (CSA, ionic polysaccharide), P-CD, or HP-P-CD. When duloxetine, cetirizine, citalopram, amlodipine, and nefopam were tested with glycogen/p-CD and glycogen/HP-p-CD, a poor enantioselectivity was observed, probably as a result of the combination of two electrically neutral chiral... 

The same research group also used EL for the separation of a test set containing /V,/V-dimethyl-3-(2-methoxyphe-noxy)-3-propylamine (DMPA), duloxetine, propranolol, primaquine, chloroquine, and nefopam. " The same capillary type was used to perform the enantioseparations. The BGE consisted of MeOH/borax 50/50 (v/v) with pH 7.5 (DMPA and duloxetine) or 8.0 (propranolol, primaquine, chloroquine, and nefopam). The borax concentration is 30 mM for DMPA, 15mM for propranolol, 35 mM for duloxetine, and 25 mM for primaquine, chloroquine, and nefopam. The concentration of the CS is 10% (w/v, for DMPA, duloxetine, primaquine, chloroquine, and nefopam) or 8% (w/v, for propranolol). Baseline separations were obtained for A,/V-dimethyl-3-(2-methoxyphenoxy)-3-propylamine (Rs = 2.31), propranolol (Rs = 2.71), and duloxetine (Rs = 3.11). Primaquine, chloroquine, and nefopam were all partially separated with resolutions below 0.5. 

In Reference 108, Wang et al. introduced a di- -amyl L-tartrate-boric acid complex for the enantioseparation of propranolol, sotalol, esmolol, atenolol, bisoprolol, metopro-lol, terbutaline, clenbuterol, cycloclenbuterol, bambuterol, and tulobuterol. Uncoated fused-silica capillaries of 50 p,m i.d. with a total length of 53.0cm and an effective length of 45.0 cm were used. A nonaqueous BGE proved useful for the ion-pair formation and the addition of TEA enhanced the enantiomeric discrimination. When a 100-mM boric acid, 80-niM di-n-amyl L-tartrate, 50-mM TEA in MeOH BGE was used, propranolol, sotalol, esmolol, atenolol, bisoprolol, and metoprolol were baseline separated with resolutions ranging from 2.3 (sotalol) to 3.0 (propranolol). Terbutaline, clenbuterol, cycloclenbuterol, bambuterol, and tulobuterol could be baseline separated with resolutions ranging from 3.2 (bambuterol) to 4.2 (clenbuterol) using a 120-mM boric acid, 100-mM di-n-amyl L-tartrate, 50-mM TEA in MeOH BGE. 

For enantioseparation of selected /3-blockers, propranolol, metoprolol, and alpren-olol, amino acids such as L-arginine [16,17], L-lysine [16], L-aspartic acid [18], or derivatives of amino acids, /V-(3,5-dinitrobenzoyl)-/ -(-)-a -phenyl glycine, and A-(3,5-dinitrobenzoyl)-L-leucine were the most frequently used chiral selectors impregnated in TLC layer [19]. Tartaric acid was employed not only as a chiral selector impregnated in the layer, but also as the CMA [20]. The structures of these chiral selectors are presented in Figure 11.2. 

A -carbobenzyloxy)-amino acid derivatives (A(-CBZ), for example, N-CQZ-isoleucyl-L-proline (ZIP), (V-CBZ-alanyl-L-proline (ZAP), and (V-CBZ-proline (ZP). Different /3-blockers have been enantioseparated so far (propranolol, pindolol, timolol, atenolol, alprenolol, and metoprolol) using CSA as a chiral counter-ion. There is only one example in the available literature for the use of methanol/0.262 M /3-CD (35 65, v/w) for the chiral separation of labetalol and the obtained separation factor was 1.07. 

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