Ursodeoxycholic acid polarity

Scalia and Games developed a packed column SFC method for the analysis of free bile acids cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) [32]. The baseline separation of all five bile acids was achieved on a packed phenyl column with a methanol-modified carbon dioxide in less than 4 min. The elution order showed a normal-phase mechanism because the solutes eluted in the order of increasing polarity following the number of hydroxyl groups on the steroid nucleus. The method was also applied to the assay of UDCA and CDCA in capsule and tablet formulations. The method was found to be linear in the range 1.5-7.5 ng/ml (r > 0.99, n = 6). The average recoveries (n= 10) for UDCA and CDCA were 100.2% with a RSD of 1.7% and 101.5% with a RSD of 2.2%, respectively. The reproducibility of the method was less than 1.5% (n = 10) for both UDCA and CDCA. 

The physiological role for the conversion of chenodeoxychoUc acid to ursodeoxycholic acid by C. absonum or other intestinal bacteria is unknown. However, ursodeoxychoUc acid is more polar than chenodeoxycholic acid (Chapter 13) and should be less toxic to bacterial cell membranes than the latter. Indeed, C. absonum will readily grow in media containing 1 mM ursodeoxychoUc acid but not 1 mM chenodeoxychoUc acid [42]. Therefore, the epimerization of the axial 7 -hydroxyl group may represent a detoxication process for C. absonum and would provide a physiological explanation for these enzymes. 

Ursodeoxycholic acid was detected very early by Hammarsten in polar bear bile (85). It was isolated in crystalline form by Shoda (58) and characterized later by Iwasaki (84). The acid, which is the 7/3-epimer of chenodeoxycholic acid, may be prepared in good yield from 7-ketolithocholic acid by reduction with sodium in propanol according to Kanazawa et al. (86). Ursodeoxycholic acid was originally considered to be a unique constituent of bear bile but has since been detected as a minor constituent in the bile of several mammals including man (2). It is also present in human feces (52). 

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