• nitric oxide;
  • analytical chemistry;
  • lyophilization;
  • stabilization;
  • prodrugs;
  • targeted drug delivery;
  • solvate;
  • kinetics;
  • chirality;
  • chemical stability


PROLI/NO is an agent of structure XN(O)[DOUBLE BOND]NONa (X = L-prolyl) whose 2-s half-life for nitric oxide (NO) release at physiological pH makes it an excellent prodrug for localizing NO's therapeutic effects at the site of application, but a difficult one to formulate and certify as pure. Despite its extraordinary thermal and hydrolytic instability, however, PROLI/NO could be formulated as an injectable drug by dissolving it in cold 0.1 M sodium hydroxide containing 5% D-mannitol, then quickly ultrafiltering and lyophilizing it in evacuated septum vials. No evidence for decomposition was seen in the contents of these evacuated vials when stored at −20°C over a 140-day observation period, as judged by quantifying NO release in simulated infusate solutions (10 mM carbonate/bicarbonate, pH 10.5). The only hydrolysis products detected were NO, nitrite ion, proline, and N-nitrosoproline, all products of normal human physiological processes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:108–115, 2006