Skip to main content

The synthesis of 17 alpha-ethynylestradiol glucuronides by mammalian microsomes immobilised in hollow-fibres

Gilder, Vanessa, Bunch, Alan William (1998) The synthesis of 17 alpha-ethynylestradiol glucuronides by mammalian microsomes immobilised in hollow-fibres. Journal of Molecular Catalysis B-Enzymatic, 5 (1-4). pp. 379-384. ISSN 1381-1177. (doi:10.1016/S1381-1177(98)00091-5) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:17767)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/S1381-1177(98)00091-5

Abstract

Uridine 5'-diphosphate glucuronosyl transferases (UGTs, E.C.2.4.1.17) catalyse the glucuronidation of xenobiotics. The oral contraceptive 17 alpha-ethynylestradiol is partly cleared by glucuronidation on the 3 and 17 positions. These glucuronides are not commercially available and were synthesised as standards for characterisation of the metabolic profile of the drug. (I) Rat and dog microsomal suspensions were investigated, and the rates of glucuronide formation were found to be < 0.09 and 0.49 nmol min(-1) mg(-1) protein, respectively. Therefore, dog microsomes were selected and immobilised in hollow-fibre membrane bioreactors. (2) Two bioreactors (15-ml capacity) were run at 20 degrees C and fed with a saturated solution (3.3 pmol/mg protein) of the sparingly soluble drug and co-factor UDPGA (0.15 mmol/mg protein) in recycle and single pass modes, at a flow rate of 20 ml/h. The recycle mode produced more glucuronide than the single pass up to 46 h (substrate to product peak area ratios of 1.6 and 5.9, respectively). The recycle mode was adopted and the bioreactors run continuously for 88 h. (3) A second batch using the same bioreactor was run for 120 h. The estimated conversion reduced from 50% on the first run to 25% on the second run. (4) A primary clean up was effected by adsorption on octadecyl silyl resin. Separation of the glucuronides from 17 alpha-ethynylestradiol was on a normal phase high pressure liquid chromatography (HPLC) system. After collection of the glucuronide fraction, the solvents were evaporated off providing 1 mg of the two glucuronides (recovery efficiency > 90%).

Item Type: Article
DOI/Identification number: 10.1016/S1381-1177(98)00091-5
Additional information: 3rd International Symposium on Biocatalysis and Biotransformations (BIOTRANS 97) LA GRANDE MOTTE, FRANCE, SEP 22-26, 1997
Subjects: Q Science > QD Chemistry
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: R.F. Xu
Date Deposited: 30 Jun 2009 12:02 UTC
Last Modified: 16 Nov 2021 09:55 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/17767 (The current URI for this page, for reference purposes)

University of Kent Author Information

Bunch, Alan William.

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.