Evaluation of rapamycin chemical stability in volatile-organic solvents by HPLC

Rapamycin or sirolimus is a carboxylic lactone-lactam macrolide with a potent immunosuppressive activity. It can be successfully used to impregnate stents inserted in coronary arteries during surgical applications, preventing fatal infection and rejection adverse effect. The chemical stability of rapamycin in several organic-volatile solvents (acetone, chloroform, dichloromethane, hexane, ethyl alcohol, ethyl acetate, methyl alcohol, pentane and tetrahydrofurane) was established by HPLC-DAD-MS in reverse phase analysis. Results permitted to exclude rapamycin chemical degradation and to reveal a typical chemical isomerization, favoured in accordance to the solvent used. Two typical peaks appear, denominated beta and gamma, the time retention of which are, respectively, 11.3 and 15.0 min. Thanks to data recovered by NMR, spectrophotometric UV and mass analyses, it was possible to establish that both peaks correspond to two different isomeric forms of rapamycin. In addition, it was possible to establish that the relative percentage peak area varies according to the solvent and to the experimental time. The two isomeric forms are in equilibrium and each solvent concurs to differently displace this equilibrium versus one form rather than another, according to their both polarity index and aproticity. (c) 2006 Elsevier B.V. All rights reserved.