Biological activity of 5-aminolevulinic acid and its methyl ester after storage under different conditions

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2007-05, Vol.87 (2), p.67-72
• Main Authors: Kaliszewski, Miron, Kwasny, Miroslaw, Juzeniene, Asta, Juzenas, Petras, Graczyk, Alfreda, Ma, Li-Wei, Iani, Vladimir, Mikolajewska, Patrycja, Moan, Johan
• Format: Article
• Language: English
• Subjects: 5-Aminolevulinic acid; ALA esters; Aminolevulinic Acid - chemical synthesis; Aminolevulinic Acid - chemistry; Drug Stability; Esters; Hydrogen-Ion Concentration; Kinetics; Photochemotherapy; Photodynamic therapy; Protoporphyrin IX; Protoporphyrins; Stability; Temperature
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2007.01.003

5-Aminolevulinic acid (ALA) is a natural precursor of protoporphyrin IX (PpIX) and heme in cells. Photodynamic therapy (PDT) utilizes a metabolic imbalance in cancer cells, leading to increased PpIX generation from exogenous ALA. Due to chemical instability of ALA in therapeutic concentrations at pH values larger than 5.0 and at high temperatures, it looses its activity by spontaneous dimerization to 2,5-dicarboxyethyl-3,6-dihydropyrazine (DHPY). ALA esters are now supplementing ALA in PDT, but little is known about their stability. We have studied the stability of ALA and its methyl ester (MAL) stored under different conditions (temperatures, pH values) by measuring their ability to generate PpIX. 100 mM solutions of both compounds were found to be stable at pH 4 and at 4 °C. However, at pH 5.5 they lost almost 10% of the initial activity during 5 days of storage at 4 °C. The fastest decay of ALA and MAL was seen at pH 7.4 and at 37 °C, and followed first order kinetics. At pH 7.4 and at 4 °C MAL lost its PpIX producing ability more slowly than at 37 °C. Our work shows that solutions should be prepared immediately before use and stored at low temperatures. The pH of stock solutions should not exceed 5.