Midodrine hydrochloride is a peripheral alpha(1)-adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2-position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD-H, Chiralcel OD-R, and alpha(1)-AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD-H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac-midodrine and each separated enantiomer, rac-deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by alpha(1)-AGP stationary phase, while the hydrolysis of rac-midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl-beta-cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests confirmed that the activity of the drug and metabolite is due only to the (-)-enantiomer because neither of the (+)-enantiomers is active. (C) 2004 Wiley-Liss, Inc.

Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent / Quaglia, Maria Giovanna; A., Farina; Palmery, Maura; Desideri, Nicoletta; E., Donati; E., Bossu'; Strano, Stefano. - In: CHIRALITY. - ISSN 0899-0042. - STAMPA. - 16:6(2004), pp. 356-362. [10.1002/chir.20041]

Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent

QUAGLIA, Maria Giovanna;PALMERY, Maura;DESIDERI, Nicoletta;STRANO, Stefano
2004

Abstract

Midodrine hydrochloride is a peripheral alpha(1)-adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2-position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD-H, Chiralcel OD-R, and alpha(1)-AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD-H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac-midodrine and each separated enantiomer, rac-deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by alpha(1)-AGP stationary phase, while the hydrolysis of rac-midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl-beta-cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests confirmed that the activity of the drug and metabolite is due only to the (-)-enantiomer because neither of the (+)-enantiomers is active. (C) 2004 Wiley-Liss, Inc.
chiral chromatography; deglymidodrine; midodrine; pure enantiomer; racemates
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Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent / Quaglia, Maria Giovanna; A., Farina; Palmery, Maura; Desideri, Nicoletta; E., Donati; E., Bossu'; Strano, Stefano. - In: CHIRALITY. - ISSN 0899-0042. - STAMPA. - 16:6(2004), pp. 356-362. [10.1002/chir.20041]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/232970
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