Kurmi Moolchand, Kushwah Bhoopendra Singh, Sahu Archana, Narayanam Mallikarjun, Singh Saranjit
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India.
Biocon-BMS R&D Centre, Bangalore 560099, India.
J Pharm Biomed Anal. 2016 Jun 5;125:245-59. doi: 10.1016/j.jpba.2016.03.039. Epub 2016 Mar 21.
This study focused on drug-drug interaction behaviour among lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), the two anti-retroviral drugs. Apart from pre-known degradation products of individual drugs, a total of twelve interaction products were detected by high performance liquid chromatography (HPLC) using a C18 column as the stationary phase, and methanol and ammonium formate in gradient mode as the mobile phase. The same HPLC method was employed for liquid chromatography-high resolution mass spectrometry (LC-HRMS) and liquid chromatography-multi stage mass spectrometry (LC-MS(n)). For the characterization of interaction products, stability samples were subjected to LC-HRMS, LC-MS(n) and online hydrogen/deuterium exchange studies. Two isomeric interaction products were isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR) studies. The collated information was utilized for the characterization of all twelve interaction products of the two drugs. Pathway of their formation was also outlined.
本研究聚焦于两种抗逆转录病毒药物拉米夫定（3TC）和替诺福韦酯（TDF）之间的药物相互作用行为。除了各药物已知的降解产物外，使用C18柱作为固定相，甲醇和甲酸铵以梯度模式作为流动相，通过高效液相色谱（HPLC）共检测到12种相互作用产物。相同的HPLC方法用于液相色谱 - 高分辨率质谱（LC - HRMS）和液相色谱 - 多级质谱（LC - MS(n)）。为了表征相互作用产物，对稳定性样品进行了LC - HRMS、LC - MS(n)和在线氢/氘交换研究。分离出两种异构体相互作用产物并进行了一维和二维核磁共振（NMR）研究。整理后的信息用于表征这两种药物的所有12种相互作用产物。还概述了它们的形成途径。
