College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Republic of Korea; Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology, 33 Dongin-ro, Jinju, 52725, Republic of Korea.
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Republic of Korea.
J Pharm Biomed Anal. 2018 Feb 5;149:374-380. doi: 10.1016/j.jpba.2017.11.005. Epub 2017 Nov 13.
The chemical stability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a therapeutic agent for neutropenia, was investigated using a validated stability-indicating reversed phase high-performance liquid chromatographic (RP-HPLC) method. 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. The method was validated for linearity, accuracy and precision over the concentration range of 0.7813-100μg/mL (r=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 110kJ/mol in the thermal conditions. Additionally, PLAG with a t of about 400h was very stable at room temperature. Therefore, PLAG was considerably influenced by alkaline and acidic hydrolysis, and thermal degradation.
1-棕榈酰-2-亚油酰-3-乙酰-rac-甘油（PLAG）是一种治疗中性粒细胞减少症的药物，本研究采用经验证的专属性反相高效液相色谱（RP-HPLC）法考察了其化学稳定性。在水解（碱性、酸性和各种 pH 缓冲液）、氧化、光解和热等应激条件下对 PLAG 进行强制降解。建立并验证了一种简单、灵敏、专属性强、耐用、精密且准确的 RP-HPLC 法，用于评估 PLAG 的降解动力学。对各种参数（如系统适用性、检测限、定量限、线性、准确度、精密度、特异性、耐用性和稳定性）进行了色谱验证。该方法在 0.7813-100μg/mL 浓度范围内进行了线性、准确度和精密度验证（r=0.9999）。所提出的方法提供了 PLAG 的良好稳定性研究结果，表明降解产物与药物完全分离。在所有实验条件下，PLAG 的降解均符合一级动力学。与中性条件相比，PLAG 在碱性和酸性条件下的降解速度更快。与水解和热条件相比，PLAG 在光解和氧化条件下相对稳定，尽管在这些条件下该药物也不稳定。在高温下，PLAG 的降解速度更快。从 Arrhenius 图评估的活化能约为 110kJ/mol，表明其在热条件下的降解速度较快。此外，PLAG 在室温下 t1/2 约为 400h，稳定性非常好。因此，PLAG 受碱性和酸性水解以及热降解的影响较大。
