Chiral high performance liquid chromatography entecavir optical isomer impurities.docVIP

 PAGE \* MERGEFORMAT 13 Chiral high performance liquid chromatography entecavir optical isomer impurities Study: YAO Tong-Wei Wang Wenna Denggui Feng Zhang Lingdi [Abstract] Chiralpak AD H chiral column (250 mm × 4.6 mm, 5 μm), to establish a normal phase high performance liquid chromatography (NP HPLC) method with direct split entecavir method of optical isomers. The effects of mobile phase composition, pH of the column efficiency, separation, retention time and other parameters. After optimization, ethanol, isopropanol hexane TFA triethylamine (70:12:18:0.05:0.05, V / V) as the mobile phase, flow rate 0.5 mL / min; detection wavelength 261 nm. Under these conditions, entecavir and separation of optical isomersgt; 4.2; optical isomers detection limit of 0.12 mg / L, at 0.25 ~ 4.0 mg / L concentration range with good linearity; day and inter-day precision RSD lt;4.0%; calculated by standard addition method, average recovery 87.0% ~ 100.8% in between; RSD lt;3.0%; by external standard method, recovery rate of 98.2% ~ 110.4% in between; RSD lt;3.0%. This method can be used as raw material drug entecavir optical isomer impurity limit control. [Keywords:] entecavir, optical isomers, HPLC, chiral separation 1 Introduction Chronic hepatitis B virus infection has been a global public health problem, developing anti-HBV drugs also has been a hot spot. At present, the clinical application of antiviral drugs are two types: @ interferon and nucleoside or nucleotide analogues , including lamivudine, adefovir, and acyclovir [1,2] .2005 March the U.S. FDA approved a new generation of anti-HBV nucleoside analogues entecavir (entecavir, ETV, trade name Baraclude) listing [3]. Entecavir is a guanine nucleotide analogues (Figure 1), Figure 1 entecavir and optical isomers of the chemical structure Fig.1 Structures of entecavir and its optical isomer in the role of kinase activity in vivo formation of triphosphate compounds, antagonistic HBV natural substrate req