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Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases

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An Erratum to this article was published on 21 October 2006

Abstract

We separated and characterized the enantiomers of bambuterol (5-[-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride), which is used in racemic form as a prodrug of terbutaline, a β2-adrenoceptor agonist. The enantioseparation was attempted on several chiral HPLC columns, and the most effective separation was achieved on the amylose-based Chiralpak AD column. Since in vivo conversion of bambuterol into terbutaline involves hydrolysis by butyrylcholinesterase (EC 3.1.1.8), we studied the reaction of enantiomers with eight human BChE variants. Both enantiomers inhibited all studied BChE variants; however, the rate of inhibition with the (R)-enantiomer was about five times faster than with the (S)-enantiomer. (R)-bambuterol inhibition rate constants for homozygous usual (UU), fluoride-resistant (FF) or atypical (AA) variant ranged from 6.4 to 0.11 min-1μM-1. The inhibition rates for heterozygotes were between the respective constants for the corresponding homozygotes.

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Acknowledgements

We wish to thank AstraZeneca for providing us with racemic bambuterol as well as Dr. R.T. Evans and Dr. O. Lockridge for providing us with rare serum specimens. This work was supported by the Ministry of Science, Education and Sports of the Republic of Croatia.

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Authors and Affiliations

  1. Ruđer Bošković Institute, Bijenička cesta 54, 10002, Zagreb, Croatia

    Ivana Gazić & Vladimir Vinković

  2. Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia

    Anita Bosak, Goran Šinko & Zrinka Kovarik

Authors
  1. Ivana Gazić
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  2. Anita Bosak
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  3. Goran Šinko
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  4. Vladimir Vinković
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  5. Zrinka Kovarik
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Corresponding author

Correspondence to Zrinka Kovarik.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00216-006-0864-9

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Gazić, I., Bosak, A., Šinko, G. et al. Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases. Anal Bioanal Chem 385, 1513–1519 (2006). https://doi.org/10.1007/s00216-006-0566-3

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  • DOI: https://doi.org/10.1007/s00216-006-0566-3

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