title: Isolation, LC-MS/MS and 2D-NMR characterization of alkaline degradants of tenofovir disoproxil fumarate.
abstract: The present work describes the preparative isolation and characterization of two alkaline degradation products of tenofovir disoproxil fumarate (TDF). Tenofovir disoproxil is a prodrug of tenofovir (antiviral agent) and co-crystal form of this prodrug with fumaric acid is tenofovir disoproxil fumarate. The drug is subjected to alkaline degradation with 0.1N sodium hydroxide for 2 min at room temperature. The two degradants were detected by high performance liquid chromatography (HPLC) at relative retention of 0.26 and 0.73 with respect to the drug. HPLC method involves gradient elution on Kromasil Eternity column (150 mm × 2.1 mm, 2.5 μm) using ammonium acetate (10mM) - acetonitrile as mobile phase at flow rate of 0.3 mL/min and UV detection at 260 nm. Two degradation products were isolated by preparative HPLC and further characterized by LC-MS, (1)H NMR, (13)C NMR and 2D-NMR. On the basis of this spectral data, the structure of two DPs are confirmed as methyl hydrogen ({[1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonate for DP-I and dimethyl ({[1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonate for DP-II.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Anandgaonkar
authors.affiliation: Analytical Chemistry Division, Daiichi Sankyo Life Sciences Research Centre in India (RCI), Gurgaon 122015, India. Electronic address: abhishek.gupta.i6@dsin.co.in.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Analytical Chemistry Division, Daiichi Sankyo Life Sciences Research Centre in India (RCI), Gurgaon 122015, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kona
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India. Electronic address: narendra.talluri@gmail.com.
authors.forename: M V N Kumar
authors.initials: MV
authors.lastname: Talluri
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D063065:Organophosphonates / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry; D012972:Sodium Hydroxide / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods; D000068698:Tenofovir
chemical_list: D063065:Organophosphonates; D011355:Prodrugs; D012972:Sodium Hydroxide; D000068698:Tenofovir; D000225:Adenine
keywords: 2D-NMR; LC–MS; Preparative HPLC; Stress degradation; Tenofovir disoproxil fumarate