Tetracyclines epimerisation

Fig. 11.9.6 has proved to be particularly useful for the analysis of impurities in commercial preparations. It is known that tetracyclins epimerise at relatively low pH values and care must be taken not to produce artifactual peaks during chromatographic procedures. 

In acidic conditions the tetracyclines undergo epimerisation at carbon atom 4 to form an equilibrium mixture of tetracycline and the epimer, 4-epi-tetracycline (Scheme 4.7). The 4-epi-tetracycline is toxic and its content in medicines is restricted to not more than 3%. The epimerisation follows the kinetics of a first-order reversible reaction (see equation (4.24)). The degradation rate is pH-dependent (maximum epimerisation occurring... 

The epimerisation of tetracycline (see section 4.1.3) is an example of a first-order reversible decomposition reaction. 

Loss of activity of solutions of some dmgs such as the tetracyclines can occur because of epimerisation of the dmg molecule, while others such as vitamin A lose activity because of geometrical isomerisation. 

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