Degradation Kinetics of Indocyanine Green in Aqueous Solution VISHAL SAXENA, 1 MOSTAFA SADOQI, 2 JUN SHAO 1 1 Department of Pharmacy and Administrative Sciences, College of Pharmacy and Allied Health Professions, St. John’s University, 8000 Utopia Parkway, Jamaica, New York 11439 2 Department of Physics, St. John’s College of Liberal Arts and Sciences, St. John’s University, 8000 Utopia Parkway, Jamaica, New York 11439 Received 14 January 2003; revised 1 May 2003; accepted 2 May 2003 ABSTRACT: The degradation kinetics of a near-infrared fluorescent, diagnostic, and photodynamic agent, indocyanine green (ICG), was investigated in aqueous solution by steady-state fluorescence technique. The influence of ICG concentration on its fluore- scence spectrum was determined. The degradation kinetics of ICG in aqueous solution was studied as a function of light exposure, type of light exposed, temperature, and ICG concentration. The degradation of ICG was found to follow first-order kinetics. Exposure to light and high temperatures caused acceleration in the degradation. The type and intensity of exposed light also affected degradation. ICG aqueous solutions were found to be more stable in dark, at low temperatures, and at higher ICG concentrations. ß 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2090– 2097, 2003 Keywords: stability; degradation kinetics; fluorescence spectroscopy; near-infrared spectroscopy; indocyanine green INTRODUCTION Current studies of the near-infrared (IR) fluores- cence agents have proven their usefulness in numerous analytical and diagnostic applications. These agents strongly absorb in the near-IR re- gion of the spectrum leading to a strong near-IR fluorescence emission, thus enabling their precise and accurate detection. Their use as biomarkers for in vivo imaging exhibits a particular advan- tage of enhanced selectivity. Because most of the biomolecules neither absorb nor emit in the near- IR region, the signals emitted by the near-IR fluorescence agents are relatively free of intrinsic background interference. Indocyanine green (ICG) is a tricarbocyanine dye, which absorbs and emits in the near-IR region of spectrum. It has been approved by the United States Food and Drug Administration for medical diagnostic studies, and has been widely used for the evaluation of cardiac output, liver function, microcirculation of skin flaps, visualization of retinal and choroidal vasculatures, pharmacoki- netic analysis, object localization in tissue, tissue welding, fluorescence probing of enzyme and proteins. All the above-mentioned uses of ICG are based on its fluorescing ability. 1,2 The chemical structure of ICG is shown in Figure 1. Moreover, ICG has a great potential for applica- tion in photodynamic therapy, which also utilizes its fluorescing ability. 3 An important motivation for using ICG in such studies is its strongest ab- sorption band around 800 nm and its most intense emission around 820 nm. 4,5 These are the wave- lengths for which the blood and other tissues are relatively transparent and the penetration depth of light in biological tissue is the highest. 6 2090 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 10, OCTOBER 2003 Correspondence to: Jun Shao (Telephone: 718-990-2510; Fax: 718-990-6316; E-mail: shaoj@stjohns.edu) Journal of Pharmaceutical Sciences, Vol. 92, 2090–2097 (2003) ß 2003 Wiley-Liss, Inc. and the American Pharmacists Association