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Application of carbohydrate based chiral stationary phase for resolution of  fenoterol, clinically used chiral drug

Małgorzata Lisowska Kuźmicz 1Zdzisław Chilmonczyk 1Anna Jończyk 1Małgorzata Kantor-Boruta 1Joanna Siedlecka 1Aleksander P. Mazurek 1,2Agnieszka Ocios-Bębenek 1

1. Narodowy Instytut Lekow (NIL), Chełmska 30/34, Warszawa 00-725, Poland
2. Medical University of Warsaw, Department of Drug Chemistry, Banacha 1, Warszawa 02-097, Poland

Abstract

Fenoterol is a sympathomimetic directly stimulating bronchial β2-adrenoreceptors [1] used in bronchial obturations. It also is widely used as a tocolytic drug in cases of imminent preterm labour for disruption of uterine contractions [2]. Recently it has been demonstrated that the β2-AR agonist activity resides primarily with (R,R)-fenoterol while (S,S)-fenoterol is essentially inactive at this receptor [3]. This compound was already resolved into pairs of enantiomers on carbohydrate stationary phases. 

  Here we report new validated method for direct chromatographic resolution of (R,R) and (S,S) fenoterol diastereoisomers on  amylose tris(3,5-dimethylphenylcarbamate), offering baseline separation of this compound  (resolution factor RS of 3.89). LOD and LOQ for the analysis were determined as 0.2 and 0.5 microgram per mililiter respectively.

  1.  Anderson S. D., Rozea P. J., Dolton R., Lindsay D. A. Inhaled and oral bronchodilator therapy in exercise induced asthma. Aust. N. Z. J. Med. 5, 544-550 (1975).
  2. Tejkalová H., Benesová O., Kristofíková Z., Binková B., Dlohozková N., Buresová M. The assessment of the behavioural teratogenic risk of the tocolytic drug phenoterol. Homeost. Health Dis. 33, 89-93 (1991).
  3. Beigi F., Bertucci C., Zhu W., Chakir K., Wainer I. W., Xiao R. P., Abernethy D. R. Enantioselective separation and online affinity chromatographic characterization of R,R- and S,S-fenoterol. Chirality 18, 822-827 (1006).
 

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Related papers

Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Małgorzata Lisowska Kuźmicz
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 12:13
Revised:   2010-03-27 15:55