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Evaluation of degradation kinetics and physicochemical stability of tenofovir
Author(s) -
Agrahari Vivek,
Putty Sandeep,
Mathes Christiane,
Murowchick James B.,
Youan BiBotti C.
Publication year - 2015
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.1656
Subject(s) - chemistry , degradation (telecommunications) , mass spectrometry , hydrogen peroxide , crystallinity , chromatography , nuclear chemistry , kinetics , hydrolysis , tenofovir , arrhenius plot , human immunodeficiency virus (hiv) , organic chemistry , activation energy , medicine , telecommunications , physics , family medicine , quantum mechanics , crystallography , computer science
Tenofovir (TFV) has been proven to prevent the transmission of the Human Immunodeficiency Virus (HIV) through the vagina. But, there is little information available about its stability under various storage and stress conditions. Hence, this study aimed to investigate the degradation behavior and physicochemical stability of TFV using liquid chromatography coupled mass spectrometry (LC‐MS) and solid state X‐ray diffraction (XRD) analyses. The LC‐MS analysis was performed on a QTrap mass spectrometer with an enhanced mass spectrum (EMS) scan in positive mode. A reversed phase C 18 column was used as the stationary phase. TFV exhibited degradation under acidic and alkaline hydrolytic conditions. The degradation products with m/z 289.2 and 170 amu have been proposed as 6‐Hydroxy adenine derivative of TFV, and (2‐hydroxypropan‐2‐yloxy) methylphosphonic acid, respectively. A pseudo‐first‐order degradation kinetic allowed for estimating the shelf‐life, half‐life, and time required for 90% degradation of 3.84, 25.34, and 84.22 h in acidic conditions, and 58.26, 384.49, and 1277.75 h in alkaline conditions, respectively. No significant degradation was observed at pH 4.5 (normal cervicovaginal pH) and oxidative stress conditions of 3% and 30% v/v hydrogen peroxide solutions. The shelf life of TFV powder at room temperature was 23 months as calculated by using an Arrhenius plot. The XRD pattern showed that the drug was stable and maintained its original crystallinity under the accelerated and thermal stress conditions applied. Stability analyses revealed that the TFV was stable in various stress conditions; however, formulation strategies should be implemented to protect it in strong acidic and alkaline environments. Copyright © 2014 John Wiley & Sons, Ltd.