title: Stability behaviour of antiretroviral drugs and their combinations. 2: Characterization of interaction products of lamivudine and tenofovir disoproxil fumarate by mass and NMR spectrometry.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India.
authors.forename: Moolchand
authors.initials: M
authors.lastname: Kurmi
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India.
authors.forename: Bhoopendra Singh
authors.initials: BS
authors.lastname: Kushwah
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Sahu
authors.affiliation: Biocon-BMS R&D Centre, Bangalore 560099, India.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Narayanam
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160 062 Punjab, India. Electronic address: ssingh@niper.ac.in.
authors.forename: Saranjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D004359:Drug Therapy, Combination; D019259:Lamivudine / Q000008:administration & dosage / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D013607:Tablets; D000068698:Tenofovir / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D044966:Anti-Retroviral Agents; D013607:Tablets; D019259:Lamivudine; D000068698:Tenofovir
keywords: Interaction products; Lamivudine; Solid state stress; Tenofovir disoproxil fumarate