Purpose: The purpose of this study is to investigate the chemical stability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a therapeutic agent for neutropenia, using a validated stability-indicating reversed phase high-performance liquid chromatographic (RP-HPLC) method.
Methods: The forced degradation of PLAG was carried out under the stress conditions of hydrolysis (alkaline, acidic and various pH buffers), oxidation, photolysis and heat. A simple, sensitive, specific, robust, precise and accurate RP-HPLC method was developed and validated for evaluating the degradation kinetics of PLAG. The chromatographic validation of various parameters, such as system suitability, detection limit, quantification limit, linearity, accuracy, precision, specificity, robustness and stability, was achieved.
Results: The method was validated for linearity, accuracy and precision over the concentration range of 0.7813–100 μg/mL (r2 = 0.9999). The proposed method provided excellent stability study of PLAG indicated by the resolution of degradation products from the drug. Degradation of PLAG provided first order kinetics under all experimental conditions. PLAG was catalysed more rapidly in alkaline and acidic conditions than in neutral conditions. PLAG was relatively stable in photolytic and oxidative conditions compared to hydrolysis and thermal conditions, although this drug was not also stable in these conditions. Exposed to high temperature, PLAG was more rapidly catalysed. The activation energy evaluated from the Arrhenius plot was about 110 kJ/mol in the thermal conditions. Additionally, PLAG with a t1/2 of about 400 h was very stable at room temperature.
Conclusion: Therefore, PLAG was considerably influenced by alkaline and acidic hydrolysis, and thermal degradation.
Eun Su Yang– College of Pharmacy, Hanyang University, South Korea
Dong Shik Kim– Hanyang University, Ansan
Jung Suk Kim– Hanyang University, Ansan
Ji Eun Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min-Jong Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min Hyun Sung– Student, Yeungnam University, Gyeongsan
Chul Soon Yong– College of Pharmacy, Yeungnam University, South Korea
Jong Oh Kim– College of Pharmacy, Yeungnam University, South Korea
Sung Giu Jin– Department of Pharmaceutical Engineering, Dankook University, South Korea
Han-Gon Choi– College of Pharmacy, Hanyang University, South Korea