Stability study of the pharmaceutical substance shikonin

Alkannin and shikonin (A/S) are potent pharmaceutical substances with a wide spectrum of well-established biological activities, such as wound healing, antimicrobial, anti-inflammatory, anti-cancer and antioxidant ones [1]. A/S and their derivatives are not stable compounds. They are susceptible under light exposure [2 – 4], to heat degradation [2,4] and have the tendency to polymerize in alkaline media, polar solvents and under high temperature [5]. A/S oligomeric derivatives demonstrate decreased antimicrobial activity and solubility [5]. The stability of A/S and their derivatives during process and storage is crucial for their use as pharmaceuticals, cosmeceuticals and food additives. The aim of this study was to examine the stability of monomeric shikonin in several solvents (acetone, methanol, chloroform and n-hexane) under several conditions (light and temperature). Stability of monomeric shikonin and formation of degradation products and oligomeric compounds were investigated under the above mentioned conditions. The HPLC system (SpectraSYSTEM, Thermo Electron Corporation, USA) used was equipped with a UV-Visible detector, set at 520nm. Chromatographic separations were carried out on a C12 Synergi Max-RP column (80A, 4 µm, 150 × 4.6 mm, Phenomenex, USA). Monomeric shikonin concentration was decreased rapidly in solutions exposed to sunlight in all solvents with different rates and several photodegradation by-products were detected. In acetone solution the photo-degradation of monomeric shikonin was the fastest one, whereas in hexane solution the slowest. Shikonin concentration in samples protected from sunlight was decreased in less extent compared with those exposed to sunlight. Exposure of shikonin solutions to both cool white fluorescent and near ultraviolet lamp, resulted in decreased monomeric shikonin concentration and similar photodegration by-products with sunlight. Additionally, temperature affected monomeric shikonin stability.

Keywords: Shikonin, stability testing, photostability, alkannin, wound healing, cancer, naphthoquinone

References:

[1] Papageorgiou, V. P., Assimopoulou, A. N., Couladouros, E. A., Hepworth, D., Nicolaou, K. C. The chemistry and biology of alkannin, shikonin and related naphthazarin natural products. Angew Chem Int Ed, 1999, 38: 270 – 300.

[2] Cho, M. H., Paik, Y. S., Hahn, T. R. Physical Stability of Shikonin Derivatives from the Roots of Lithospermum erythrorhizon Cultivated in Korea. J Agric Food Chem, 1999, 47: 4117 – 4120.

[3] Cheng, H. W., Chen, F. A., Hsu, H. C., Chen, C. Y. Photochemical decomposition of alkannin/shikonin enantiomers. Int J Pharm, 1995, 120: 137 – 144

[4] Mitsui Petrochemical Industries, Information Booklet, Physical and chemical properties of shikonin

[5] Assimopoulou, A. N., Papageorgiou, V. P. Study on isohexenylnaphthazarins polymerization in alkaline media. Biomed Chromatogr, 2004, 18: 508 – 522.