Indocyanine Green: Pharmacokinetics in the Rabbit and Relevant Studies of its Stability and Purity

The plasma concentration-time profile of indocyanine green (1) in the rabbit was determined by spectrophotometric and highperformance liquid chromatographic (HPLC) analysis following doses of 5 or 25mg/kg. Spectrophotometric analysis yielded plasma concentration estimates that were higher than those obtained by an HPLC method and this difference was particularly large at time points ≥30min postdose. Chromatograms of plasma samples from each rabbit exhibited two peaks, both of which were maximal in the first postdose sample, suggesting an impurity in the commercial preparation. HPLC analysis of five different lots of 1 suggested a variable abundance of this impurity (1.7–4.0%). When stored in a variety of aqueous solutions, 1 degraded to a compound with a retention time identical to that of the impurity. The time for 50% degradation of 1 in deionized, distilled, and sterile water was 19, 92, and 99 h, respectively, and the rate of decay in these solvents exhibited significant interday variability. Dilute acetic acid (∼20mM; pH=3.2) was found to substantially accelerate this degradation (50% degradation in