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Direct enantiomeric resolution of tamsulosin, clinically used chiral O-phenylethanolamine derivative with α1-blocking activity

Anna Jończyk 1Zdzisław Chilmonczyk 1Małgorzata Kantor-Boruta 1Hanna Ksycińska 2Małgorzata Lisowska Kuźmicz 1Aleksander P. Mazurek 1Joanna Siedlecka 1Wojciech J. Szczepek 2

1. Narodowy Instytut Lekow (NIL), Chełmska 30/34, Warszawa 00-725, Poland
2. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


Tamsulosin is an α1-adrenoreceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia. It was one of the first subtype-selective α1-adrenoceptor antagonist with specificity for prostatic α1-adrenoceptors to become available for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). Benign prostatic hyperplasia is a common disease affecting elderly men (about 50%), and leads to a variety of urological symptoms. Urinary flow is influenced by many factors, particularly by prostatic and urethal smooth muscle tone, which is mainly controlled by α1-adrenoceptors. The medical treatment of BPH is amongst others directed towards the use of agents that block those receptors. It has been reported that in rabbit lower urinary tract and prostate preparations (R)-enancjomer of tamsulosin was 50-141 times more potent than (S)-enantiomer [1].

Here we report 3 methods for direct chromatographic determination of (R)- and (S)-tamsulosin  on two carbohydrate - amylose tris(3,5-dimethylphenylcarbamate) and tris-(S)-1-phenylethyl- carbamate - and on β-cyclodextrine bound chiral stationary phases (RS ≥ 2.69). Employed mobile phases were hexane-ethanol-ethanolamine (80:20:0.2) for  amylose tris(3,5-dimethylphenyl- carbamate), hexane-ethanol-diethylamine (75:25:0,025) for amylase tris-(S)-1-phenylethylcarbamate and phosphate buffer (pH 7.0)-acetonitrile (65:35) for cyclodextrine stationary phase. The elution order of enantiomers was (S) before (R) on carbohydrate and (R) before (S) on cyclodextrine stationary phases. It should be noted that on cellulose tris(3,5-dimethylphenylcarbamate) only poor enantioresolution hase been obtained (RS between 0.57 and 0.93). That would suggest that helical amylose structure should be important for the enantiodifferentiation [3].

1.      Honda, K., Nakagawa, C. Alfa-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 in rabbit lower urinary tract and prostate. J. Pharmacol. Exp. Ther. 239(2): 512-516, 1986.

2.      Z. Chilmonczyk, Ł. Sienicki, B. Łozowicka, M. Lisowaka-Kuźmicz,  A. Jończyk, H. Y. Aboul-Enein. „Structure-retention relationship in a series of chiral 1,4-disubstituted piperazine derivatives on carbohydrate chiral stationary phases”. Farmaco 60, 439-443 (2005).


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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Anna Jończyk
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 08:42
Revised:   2010-04-05 00:02