Stability behaviour of antiretroviral drugs and their combinations. 3: Characterization of interaction products of emtricitabine and tenofovir disoproxil fumarate by mass spectrometry

[Display omitted] •Interaction between FTC and TDF explored in powder mixtures and marketed FDC formulation.•Six novel interaction products detected by HPLC-PDA.•Structures of interaction products identified by LC-HRMS, LC–MSn and online H/D exchange studies.•Pathway of drug–drug interaction outlined. The present study investigated drug–drug interaction behaviour of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) under solid state stability test conditions. Six interaction products were separated and detected by high performance liquid chromatography coupled to photodiode array detector (HPLC-PDA) using C18 column. The same were characterized using LC-high resolution mass spectrometry (LC-HRMS), LC-multi stage mass spectrometry (LC–MSn) and online hydrogen/deuterium (H/D) exchange studies. The interaction pathway among the two drugs was outlined based on the elucidated structures. Four of the six interaction products were also formed in marketed tablets containing FTC and TDF (along with efavirenz (EFV)) that were kept without packing under accelerated condition of 40°C/75% RH till 6 months.