Resolution of the enantiomers of racemic atenolol, metoprolol, propranolol, and labetalol, commonly used β-blockers, has been achieved by TLC on silica gel plates using vancomycin as chiral impregnating reagent or as chiral mobile phase additive. With vancomycin as impregnating agent, successful resolution of the enantiomers of atenolol, metoprolol, propranolol, and labetalol was achieved by use of the mobile phases acetonitrile-methanol-water-dichloromethane 7:1:1:1 (
), acetonitrile-methanol-water 6:1:1 (
), acetonitrile-methanol-water-dichloromethane-glacial acetic acid 7:1:1:1:0.5 (
), and acetonitrile-methanol-water 15:1:1 (
), respectively. With vancomycin as mobile phase additive, successful resolution of the enantiomers of metoprolol, propranolol, and labetalol was achieved by use of the mobile phases acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5) 6:1:1 (
), acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5) 15:1:2 (
), and acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5)-dichloromethane 9:1:1.5:1 (
), respectively. Spots were detected by use of iodine vapor. The detection limits were 1.3, 1.2, 1.5, and 1.4 μg for each enantiomer of atenolol, metoprolol, propranolol, and labetalol, respectively.
Authors:Massoumeh Shafiei, Gholamreza Omrani, and Massoud Mahmoudian
The internal mammary artery (IMA) is currently the preferred conduit for myocardial revascularization. However, perioperative vasospasm and a hypoperfusion state during maximal exercise may limit its use as a bypass graft. The mechanism of spasm has not been clearly defined. Since beta-adrenoceptor activation plays a major role in vasorelaxation, the present study was carried out to investigate the beta-adrenoceptor responsiveness of human IMA smooth muscle. Isoproterenol produced a concentration-dependent relaxation in endothelium-denuded IMA segments, precontracted with phenylephrine (maximal relaxation 46.33....5.45%). Atenolol (10 –6 M) and propranolol (2×10 –7 M) inhibited isoproterenol-induced relaxation. While atenolol produced partial inhibition, propranolol caused a complete inhibition in a majority of the segments and a partial inhibition in a minority. BRL 37344, a selective beta 3-adrenoceptor agonist, produced a concentration-dependent relaxation in phenylephrine-precontracted rings of endothelium-denuded IMA (maximal relaxation 40.35....4.07%). Cyanopindolol, a beta-adrenoceptor partial agonist, produced a marked relaxation (58.65....6.2%) in endothelium-denuded IMA rings, precontracted with phenylephrine. Cyanopindolol-induced relaxation was resistant to blockade by propranolol (2×10 –7 M). Spontaneous contractions of IMA rings were also observed in some cases that were inhibited by isoproterenol and BRL 37344. This observation implies the important role of beta-adrenoceptor activation in prevention of human IMA spasm.
Authors:Ravi Bhushan, Jürgen Martens, Charu Agarwal, and Shuchi Dixit
Cu(II) complexes of L-threonine, L-serine, and L-tartaric acid were prepared and used as ligand exchange reagents for enantiomeric resolution of some of the β-blockers (bisoprolol, metoprolol, and propranolol) and a β2-agonist (salbutamol). Impregnated thin-layer plates were prepared by spreading slurry of silica gel prepared in the solutions of each of the three ligand exchange reagents. The spots were detected with iodine. Effect of temperature on enantioresolution was also studied. The detection limits were found in the range 0.19–0.26 μg for each enantiomer. L-Ser proved to be a good ligand using a common mobile phase in each case.
An isothermal titration calorimetry (ITC) method
to measure the heat effects evolving from the binding between cation exchanger
Amberlite IRP 69 and the cationic drug substances propranolol hydrochloride
(PROP), metoprolol tartarate (METO), acebutolol hydrochloride (ACEB) and chlorpheniramine
maleate (CPR) has been developed. The method gives repeatable results with
an error about 5% for the beta-blockers PROP, METO and ACEB, and about 10%
for the antihistamine CPR.
The calculation of the thermodynamic parameters enthalpy
and Gibbs free energy change (ΔGbind)
show significant differences between the different drug substances.
Authors:A. K. Shakya, N. M. Hakooz, T. A. Arafat, A. N. A. Abu-Awwad, J. A. El-Ghani, and M. Melhim
A sensitive and specific high-performance liquid chromatographic-electrospray ionization tandem mass spectrometric (HPLC-ESI-MS-MS) method for quantification of tamsulosin in human plasma, using propranolol as internal standard (IS), has been developed, validated successfully, then used in a clinical study. Plasma (0.5 mL) was mixed with 50 μL 1 m sodium carbonate solution. Tamsulosin and propranolol were isolated from the mixture by liquid-liquid extraction with 7:3 (v/v) hexane-ethyl acetate. Reversed-phase chromatography was performed on a C8 column at 25°C with 70:30:0.1 (v/v) methanol-water-formic acid as mobile phase at a flow-rate of 1.0 mL min−1. Quantification was achieved in positive-ion mode by monitoring the product ions at m/z 409.1 → 270.9, 228.0, and 200.0 (tamsulosin) and m/z 260.1 → 183.0 (IS). The lowest limit of quantification was 0.25 ng mL−1, and the calibration range was 0.25–50 ng mL−1. Within and between batch precision (expressed as coefficient of variation, CV) did not exceed 10.8% and accuracy was within 5.0% deviation of the nominal concentration. Recovery of tamsulosin from plasma was >83.0%. The validated method was used for clinical study of tamsulosin in human volunteers.
A chromatographic-densitometric method has been established for identification and quantitation of selected beta-adrenergic-blocking agents in pharmaceutical preparations. Retention factors,
, and characteristic absorption spectra of 11 drugs chromatographed on silica gel 60 F
HPTLC plates with six mobile phases were used for identification. Quantitation and validation of the method was performed for atenolol, acebutolol, propranolol, and bisoprolol using chloroform-methanol-ammonia, 15 + 7 + 0.2 (
), as mobile phase. UV densitometric measurements were performed at the wavelength of maximum absorption. Pharmaceutical preparations used in medicine and from a variety of manufacturers were analyzed and the method shown to be sufficiently sensitive for analysis of these samples. The limits of detection and determination ranged from 30 to 400 ng and recovery was from 97.14 to 102.18%. The precision of the method, described by the equation
, is good and the range of linearity is wide — from 0.020 to 0.250% for individual constituents.
Authors:N.M. Omar, A.M. Abbas, Hala Abdel-Malek, and G.M. Suddek
For evaluating the age-related change in noradrenaline (NA)-induced contraction of isolated rat carotid artery (CA), the effect of α and β adrenoreceptor (AR) blockers and the role of nitric oxide (NO) were investigated. Methods: Concentration-response curves to NA (10−10–10−4 M) and α1 agonist phenylephrine (PE; 10−10–10−5 M) were constructed in isolated CA rings from young and middle-aged rats. The effects of nitric oxide synthase (NOS) inhibitor (L-NAME; 100 μM), α1-AR antagonist (prazosin; 0.1 μM), α2-AR antagonist (yohimbine; 0.1 μM) and β-AR antagonist (propranolol; 1 μM) on NA-induced contraction of isolated CA rings were examined. In CA rings preconstricted with NA, the responses to α2-AR agonist (clonidine; 10−7–10−5 M), β-AR agonist (isoprenaline; 10−8–10−5 M),), sodium nitroprusside (SNP; 10−9–10−5 M) were assessed. Results: The maximum contractile response of CA to NA and to PE was higher in younger than in middle-aged rats. Prazosin reduced the contractile response to NA in both groups, while propranolol, yohimbine and L-NAME did not affect NA-induced contraction in either of them. Clonidine, isoprenaline and SNP produced a dose-dependent vasorelaxation of CA rings, isoprenaline-induced vasodilatation was lower in middle-aged rats, while there was no difference in clonidine or SNP-induced relaxant effect between the two groups. Conclusions: NA-induced contraction of isolated rat CA rings is decreased in old rats, this is related to α1-AR. β-AR mediated dilatation was compromised in middle-aged rats (endothelium-dependent). α2-AR and SNP-mediated dilator effect seems to be unchanged.
Authors:Beáta Szalóczi, Ágnes Harmath, Barbara Pete, Eszter Kovács, János Rigó jr., and Júlia Hajdú
A szerzők egy Basedow–Graves-kór miatt korábban thyreoidectomián átesett, kezeletlen anya koraszülöttjének esetét ismertetik. Gondozatlan terhességből magzati tachycardia, fenyegető intrauterin asphyxia miatt sürgős császármetszéssel született a 33. hétnek megfelelő érettségű, 1350 gramm súlyú, dysmaturus (testsúlypercentil <10), nagy nyaki strumával bíró koraszülött. Az újszülött respiratoricus elégtelenség miatt konvencionális és magas frekvenciás gépi lélegeztetésben részesült, súlyos tachycardia (>180/perc), cardialis decompensatio miatt béta-blokkoló, digoxin- és dobutaminterápiát igényelt. Kivizsgálása során cardiomegalia, pericardialis folyadékgyülem, súlyos tüdőhypoplasia, mitralis és tricuspidalis insufficientia, hepatosplenomegalia igazolódott. A pajzsmirigy-szabadhormonok szintje többszörösen meghaladta a referenciaértéket (fT4: > 6 ng/dl, fT3: > 30 pg/ml), a TSH-szint ugyanakkor 0 volt. Légzéstámogatást 7, keringéstámogatást 10 napig igényelt, propranolol- mellett K-jodid-kezelésben részesült. Tachycardiája mérséklődött, a béta-blokkoló kezelést csökkentett adagban kapta tovább, pajzsmirigyhormonszintjei fokozatosan a normális tartományba kerültek. A szerzők felhívják a figyelmet arra, hogy a Basedow–Graves-kórban szenvedő anya újszülöttjénél jelentős súlybeli, növekedésbeli elmaradás, súlyos keringési elégtelenség, thyreotoxicosis tünetei alakulhatnak ki, és hangsúlyozzák az anyai hormon-, valamint antitestszintek nyomon követésének jelentőségét.
Authors:D. S. Patel, N. Sharma, M. C. Patel, B. N. Patel, P. S. Shrivastav, and M. Sanyal
A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of aripiprazole in human plasma. The analyte and propranolol as internal standard (IS) were extracted from 200 μL of human plasma via liquid-liquid extraction using methyl tert-butyl ether under alkaline conditions. The best chromatographic separation was achieved on an Aquasil C18 (100 × 2.1 mm, 5 μm) column using methanol-deionized water containing 2 mM ammonium trifluoroacetate and 0.02% formic acid (65:35, v/v) as the mobile phase under isocratic conditions. Detection of analyte and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The method was fully validated for its selectivity, interference check, sensitivity, carryover check, linearity, precision and accuracy, reinjection reproducibility, recovery, matrix effect, ion suppression/enhancement, stability, ruggedness, and dilution integrity. The assay was linear over the concentration range of 0.10–100 ng mL−1 for aripiprazole. The intra-batch and inter-batch precision (%CV) was ≤4.8%, while the mean extraction recovery was >96% for aripiprazole across quality control levels. The method was successfully applied to a bioequivalence study of 10 mg aripiprazole orally disintegrating tablet formulation in 27 healthy Indian subjects under fasting and fed condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 260 incurred samples.