Mourad Sara S, El-Kimary Eman I, Hamdy Dalia A, Barary Magda A
J Chromatogr Sci. 2016 Oct 17;54(9):1560-1566. doi: 10.1093/chromsci/bmw103.
This work aims to develop HPLC-DAD method for linagliptin (LNG) quantitation in the presence of its degradation products in tablets and to study its degradation kinetics. LNG samples were extracted from tablets and diluted. Various ICH degradation conditions were applied to study LNG degradation kinetics. LNG was assayed by a C18 column using a simple isocratic mobile phase (methanol:water containing 0.3% TEA, 40:60, pH 4.5) pumped at 1 mL/min. The drug was detected at 225 nm. The method showed high linearity (r2 > 0.999) with CV% and % error of the mean <2% over the range of 1-50 μg/mL. Limits of detection and quantitation were 0.3 and 1.0 μg/mL, respectively. LNG retention time was 11 min with a total run time of 17 min. In all degradation conditions applied, LNG was well separated from its degradation products. The method was successfully used to quantitate LNG content in its tablets and study its degradation kinetics in acidic, alkaline and oxidative forced degradation experiments. In conclusion, simple, precise and reliable method for the separation and determination of LNG in the presence of its degradation products under different stress conditions was developed and validated according to the latest ICH guidelines.
本研究旨在开发一种高效液相色谱-二极管阵列检测法（HPLC-DAD），用于在存在降解产物的情况下定量测定片剂中的利格列汀（LNG），并研究其降解动力学。从片剂中提取并稀释LNG样品。应用各种国际协调会议（ICH）规定的降解条件来研究LNG的降解动力学。使用C18柱，采用简单的等度流动相（甲醇：含0.3%三乙胺的水，40:60，pH 4.5），以1 mL/min的流速泵送，对LNG进行测定。在225 nm波长处检测药物。该方法在1-50 μg/mL范围内具有高线性（r2>0.999），变异系数（CV%）和平均误差百分比<2%。检测限和定量限分别为0.3和1.0 μg/mL。LNG的保留时间为11分钟，总运行时间为17分钟。在所有应用的降解条件下，LNG与其降解产物均能很好地分离。该方法成功用于定量测定片剂中的LNG含量，并在酸性、碱性和氧化强制降解实验中研究其降解动力学。总之，根据最新的ICH指南，开发并验证了一种简单、精确且可靠的方法，用于在不同应激条件下分离和测定存在降解产物时的LNG。
