Metoprolol Ethanol

Fig. 3 Chromatograms showing analysis of disopyr-amide and mono-A -dealkyldisopyramide enantiomers in plasma (A) blank plasma, (B) plasma spiked with 625 ng/ml of disopyramide and mono-A-dealkyldiso-pyramide enantiomers, (C) plasma sample from a healthy volunteer collected 6 hr after administration of 100 mg of Dicorantil. Peak assignments 1, (5)-(+)-disopyramide 2, )-disopyramide 3,4, metoprolol 5, (5 )-(+)-mono-iV -dealkyldisopyramide and 6, (/ )-(—)-mono-A-dealkyldisopyramide. Chromatographic conditions Chiralpak AD column (250 x 4.6 mm I.D., 10 pm particle size) hexane-ethanol (91 9, v/v) mobile phase plus 0.1% diethylamine 1.2ml/min flow rate and detection at 270 nm. (From Ref 1)...

Noninterfering acetaminophen, acetylmorphine, amiodarone, amobarbital, amphetamine, bendroflumethiazide, benzocaine, benzoylecgonine, benzthiazide, butalbital, carbamaze-pine, chlorothiazide, clonazepam, cocaine, codeine, cotinine, cyclosporine, cyclothiazide, desalkylflurazepam, diamorphine, dicumerol, ephedrine, ethaciynic acid, ethanol, eth-chlorvynol, ethosuximide, furosemide, glutethimide, hydrochlorothiazide, hydrocodone, hydroflumethiazide, hydromorphone, lorazepam, mephentermine, meprobamate, meth-amphetamine, metharbital, methoxsalen, methoxyphenteramine, methsuximide, meth-ylcyclothiazide, metoprolol, MHPG, monoacetylmorphine, morphine, normethsuximide, oxazepam, oxycodone, oxymorphone, pentobarbital, phencyclidine, phenteramine, phenylephrine, phenytoin, polythiazide, primidone, prochlorperazine, salicylic acid, sulfanilamide, THC-COOH, theophylline, thiazolam, thiopental, thioridazine, tocainide, trichlo-romethiazide, trifluoperazine, valproic acid, warfarin... 

Metoprolol is used in the form of its tartrate which is soluble 1 1 in water and 1 2 in ethanol. 

Enantiomers of (-P/—)-metoprolol tartrate were separated on silica gel 60F plates using the chiral selector d-(—)-tartaric acid (11.6 mM solution) both impregnated into the layer and as mobile phase additive. The mobile phase was ethanol/water (70 30) and development temperature was 25 C. The layer was impregnated at ambient temperature for 90 min before sample application. Separated zones were detected by viewing at 254 nm, scanning at 230 nm, and exposure to iodine vapor. Rf values were 0.65 and 0.50 for the S-(—) and R-(+) enantiomers, respectively [19]. 

The following chiral reagents were employed for diastereomer formation before sample application and chromatography on silica gel or silica gel G TLC plates (L)-leucine Af-carboxyanhydride for D,L-dopa-carboxyl- " C separated with ethyl acetate/formic acid/water (60 5 35) mobile phase and detected by ninhydrin [7 f 0.38 (d)/0.56 (l)] [43] Af-trifluoroacetyl-L-prolyl chloride for D,L-amphetamine separated with chloroform/methanol (197 3) and detected by sulfuric acid/formaldehyde (10 1) (Rf 0.49 (d)/0.55 (l)) [44] Af-benzyloxycarbonyl-L-prolyl chloride for D,L-methamphetamine separated with n-hexane/ethyl acetate/acetonitrile/diisopropyl ether (2 2 2 1) and detected by sulfuric acid/formaldehyde (10 1) [/ f 0.57 (l)/0.61 (d)] [44] (l/ ,2/ )-(-)-l-(4-nitrophenyl)-2-amino-1,3-propanediol (levobase) and its enantiomer dextrobase for chiral carboxylic acids separated with chloroform/ethanol/acetic acid (9 1 0.5) and detected under UV (254 nm) light R[ values 0.63 and 0.53 for 5- and / -naproxen, respectively) [45] (5)-(4-)-a-methoxyphenylacetic acid for R,S-ethyl-4-(dimethylamino)-3-hydroxybutanoate (carnitine precursor) with diethyl ether mobile phase [/ f 0.55 R)/0J9 (5)] [46] and (5)-(4-)-benoxaprofen chloride with toluene/acetone (100 10, ammonia atmosphere) mobile phase and fluorescence visualization (Zeiss KM 3 densitometer 313 nm excitation, 365 nm emission) (respective R values of R- and 5-isomers of metoprolol, oxprenolol, and propranolol were 0.24/0.28, 0.32/0.38, and 0.32/0.39) [47]. 

Also, D-(—)-tartaric acid has been used as a CMPA for the separation of ( )-metoprolol tartarate on silica gel plates preimpregnated with the mobile phase (ethanobwater, 70 30, v/v) containing D-(-)-tartaric acid as a chiral selector. The results of experiments performed with different concentrations of D-(-)-tartaric acid (5.8,11.6, and 23 mmol/1) revealed that the best resolution of the metoprolol tartarate enantiomers was achieved with 11.6 mmol/1 d-(-(-tartaric acid in both the mobile phase and the impregnation solution at 25 2" C. It has been assumed that tartaric acid (p Tai 2.93) dissolved in excess of ethanol could react with ethanol forming monoethyltartrate, which might play a role of a real chiral selector in this separation system [43]. The structures of CSA, ZGP, and monoethyltartrate as counterions are presented in Figure 6.3. 

FIGURE 11.3 (a) 2,2,2-Trifluoro-l-(9-anthryl)ethanol separated on CSPl (ionic) using hexane-2-propanol (80 20). Scanned at A, = 380 nm. (b) Metoprolol separated on CSPl (ionic) using hexane-2-propanol-acetonilrile (80 15 5). Scanned at X = 410 nm. (From Wall, P.E., J. Planar Chromatogr., 2, 228,1989. With permission.)... 

Sample preparation The solutions of racemic mixtures of ( )-metoprolol at a concentration 0.01 mol/l and their pure isomers were prepared in 70% ethanol. 

Sample preparation Metoprolol solutions were prepared in 95% ethanol. 

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