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 high-performance liquid chromatographic (HPLC) analysis following doses of 5 or 25 mg/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 greater than or equal to 30 min 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 (approximately 20 mM; pH = 3.2) was found to substantially accelerate this degradation (50% degradation in less than 1 h). Interestingly, this acid-catalyzed rate of conversion of 1 to the degradation product fit about equally well assuming a zero-order or first-order process. In an effort to elucidate the structure of this degradation product (impurity), UV-visible spectra of appropriate column eluates were obtained. The spectra of these compounds differed from that of 1 in only minor details.(ABSTRACT TRUNCATED AT 250 WORDS)