• Archives of Pharmacal Research
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• v.23 no.3
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• pp.230-236
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• 2000

(1'R, 2R)-, (1'R, 2S)-, (1'S, 2R)- and (1'S, 2S)-$\alpha$-hydroxymetoprolol; (2R)- and (2S)-O-des-methylmetoprolol; and (2R)- and (2S)-metoprolol acid are major metabolites of (2R)-and (2S)-metoprolol, $\beta$-adrenergic antagonist. The focus of most chiral separation methods until now has been on determination of the enantiomeric parent drug. However, it is just as important to be able to follow the metabolism of the enantiomers and their possible chiral metabolites. Therefore, for the study of stereoselective metabolism and pharmacokinetics of metoprolol, the chiral separation of the enantiomers of metoprolol and its metabolites has been investigated using four chiral stationary phases, i.e., Chiralcel OD, Chiral-AGP, Cyclobond I and Sumichiral OA-4900 columns. Metoprolol acid was resolved only by Sumichiral OA-4900. Chiralcel OD provided the highest separation factor and resolution value for metoprolol and O-desmethylmetoprolol and partially resolved the four stereoisomers of $\alpha$-hydroxymetoprolol. Diastereomeric $\alpha$-hydroxymetoprolols were resolved using the coupled column chromatographic system of two chiral stationary phases, Sumichiral OA-4900 column and Chiralcel OD column.

• Archives of Pharmacal Research
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• v.23 no.3
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• pp.226-229
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• 2000

To obtain the standard compounds of metoprolol for a pharmacokinetic study, a convenient synthetic procedure to prepare enantiomers of metoprolol (3a) and its major metaboites, 2-4-(2-hydroxy-3-isopropylamino)propoxyphenylathanol (3b) and 4-(2-hydroxy-3- isopropylamino) pro-poxyphenylacetic acid (4), was developed from their respective starting materials, 4-(2-methoxyethyl)phenol (1a), 4-(2-hydroxyethyl)phenol (1b) and methyl 4-hydroxyphenylacetate (1c). These phenolic compounds (1a, b, c) were converted in situ to their corresponding phenoxides with sodium hydroxide treatment followed by (R)- or (S)-epichlorohydrin treatment. The resulting epoxides 2 were transformed to 3 through reaction with isopropylamine. Ester 3c was hydrolyzed to the metabolite 4. Measured using the HPLC method on chiral column without any derivatization, the optical purity of enantiomers of metoprolol and o-demethylated metabolite 3b ranged between 96-99 ％ ee and that of enantiomers of carboxylic acid metabolite 4 ranged 91％ ee.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.117-126
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• 1999

Differential scanning calorimetry(DSC) was used as a screening technique for assessing the compatibility of some drugs with excipients. On the basis of DSC results, interaction of ibuprofen with PVP K40 was found and eutectic formations with PEG 6000 or magnesium stearate were demonstrated. Fenoprofen Ca was found to interact with PEG 6000. Naproxen showed interactions with PEG 6000, PVP K40, PVPP and Mg stearate. Interactions of tiaprofenic acid with PVP K40 or PVPP were found and eutectic formations with PEG 6000 or Mg stearate were observed. Bisoprolol hemifumarate, metoprolol tartrate and penbutolol sulfate were found to interact with lactose.

• Analytical Science and Technology
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• v.34 no.1
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• pp.9-16
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• 2021

In the group of commonly prescribed β-blocker drugs, one of the enantiomers is generally relatively more active than the others. This study aims to develop a technique for the chiral analysis of select β-blockers based on proton nuclear magnetic resonance (1H-NMR) spectrometry. (S)-2-Tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid ((S)-TBMB) was synthesized and utilized as a chiral derivatizing agent. Pure β-blocker enantiomers were isolated from racemates by semi-preparative liquid chromatography prior to derivatization. The reaction time and concentration of (S)-TBMB were controlled to improve the derivatization procedure. No racemization was found during the analysis. High-performance liquid chromatography (HPLC) analysis was also performed for comparative purposes. High agreement between the NMR and HPLC methods was achieved in the determination of (R)-metoprolol in a standard solution of the (S) isomer.