Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India.
J Pharm Biomed Anal. 2009 Dec 5;50(5):797-802. doi: 10.1016/j.jpba.2009.06.031. Epub 2009 Jun 24.
A novel stability-indicating gradient reverse phase liquid chromatographic (RP-LC) method was developed for the determination of purity of famciclovir (FCV) in presence of its impurities and degradation products. The method was developed using Inertsil ODS 3 V (250 x 4.6 mm, 5 microm) column with mobile phase containing a gradient mixture of solvent A and B. 0.01 M potassium dihydrogen orthophosphate buffer, pH adjusted to 6.0 with 1% potassium hydroxide was used as buffer. Buffer and methanol in 80:20 (v/v) ratio was used as solvent A and buffer and methanol in 20:80 (v/v) ratio was used as solvent B. The gradient program (T/%B) was set as 0/5, 15/30, 25/50, 45/60, 55/5 and 60/5. The eluted compounds were monitored at 215 nm. FCV was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. FCV was found to degrade significantly in oxidative, acid and base degradation conditions and mildly in hydrolytic degradation conditions and stable in thermal and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities thus proved the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy, robustness and system suitability. This method is also suitable for the assay of famciclovir which ranged from 99.9% to 100.2%.
建立了一种新的用于检测泛昔洛韦（FCV）纯度的稳定性指示梯度反相高效液相色谱（RP-LC）法，可同时检测其杂质和降解产物。方法采用 Inertsil ODS 3 V（250×4.6mm，5μm）色谱柱，流动相为溶剂 A 和 B 的梯度混合液。0.01 M 磷酸二氢钾缓冲液（用 1%氢氧化钾调 pH 值至 6.0）为缓冲液，甲醇和缓冲液的体积比为 80∶20（v/v）为溶剂 A，甲醇和缓冲液的体积比为 20∶80（v/v）为溶剂 B。梯度程序（T/%B）为 0/5、15/30、25/50、45/60、55/5 和 60/5。在 215nm 下检测洗脱化合物。FCV 分别在氧化、酸、碱、水解、热和光降解条件下进行了稳定性考察。结果表明，FCV 在氧化、酸和碱降解条件下显著降解，在水解降解条件下轻度降解，在热和光降解条件下稳定。降解产物与主峰及其杂质完全分离，证明该方法具有较强的专属性。该方法按照国际人用药品注册技术协调会（ICH）的指导原则进行了验证，包括专属性、检测限、定量限、精密度、线性、准确度、耐用性和系统适用性。该方法还适用于 99.9%~100.2%的 FCV 含量测定。
