抗流感药物GZ830降解规律研究
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摘要
目的建立抗流感药物GZ830含量测定及有关物质检查的高效液相色谱(HPLC)方法,并探讨其降解规律。方法采用HPLC研究GZ830在不同pH溶液和不同温度条件下的降解情况,探究其降解规律。结果建立了用于GZ830体外含量测定的HPLC方法,药物在160～1200μg/ml浓度范围内与峰面积线性关系良好(r=0.9998);GZ830在碱性条件下易降解,且不耐受高温,其水溶液在40℃条件下加热6 h主药无降解;80℃条件下加热6 h,主药降解约2.4%;115℃条件下30 min,降解约7%。结论在优化色谱条件下,GZ830与降解产物分离度良好、灵敏度高、专属性强,不同条件下的降解途径有差异。
Objective To establish an HPLC method for the determination of anti-influenza drug GZ830 and its related substances,and investigate the degradation of GZ830. Methods The degradation of GZ830 under the conditions with different pH and temperatures was investigated with HPLC method to explore the degradation principle. Results The HPLC method for the determination of GZ830 was established. The linear relationship between the drug and the peak area was good in the concentration range of 160-1200 μg/ml(r=0.9998). GZ830 was easily degraded under alkaline conditions and could not tolerate high temperatures. The degradation of GZ80 did not occur when its aqueous solution was kept at 40℃ for 6 h. However,after heating at 80℃ for 6 h,about 2.4%GZ80 was degraded and the degradation rate reached about 7% after kept at 115℃ for 30 min. Conclusion Under the optimized chromatographic conditions,GZ830 was well separated from the degraded products,and the HPLC method possessed high sensitivity and good specificity for the determination of GZ80,and the degradation of GZ80 was different under different conditions.
Objective To establish an HPLC method for the determination of anti-influenza drug GZ830 and its related substances,and investigate the degradation of GZ830. Methods The degradation of GZ830 under the conditions with different pH and temperatures was investigated with HPLC method to explore the degradation principle. Results The HPLC method for the determination of GZ830 was established. The linear relationship between the drug and the peak area was good in the concentration range of 160-1200 μg/ml(r=0.9998). GZ830 was easily degraded under alkaline conditions and could not tolerate high temperatures. The degradation of GZ80 did not occur when its aqueous solution was kept at 40℃ for 6 h. However,after heating at 80℃ for 6 h,about 2.4%GZ80 was degraded and the degradation rate reached about 7% after kept at 115℃ for 30 min. Conclusion Under the optimized chromatographic conditions,GZ830 was well separated from the degraded products,and the HPLC method possessed high sensitivity and good specificity for the determination of GZ80,and the degradation of GZ80 was different under different conditions.
引文
[1] Johansson BE,Brett IC. Changing perspective on immunization against influenza[J]. Vaccine,2007,25(16):3062-3065.
[2] de Jong JC,van Nieuwstadt AP,Kimman TG,et al. Antigenic drift in swine influenza H3 haemagglutinins with implications for vaccination policy[J]. Vaccine,1999,17(12):1321-1328.
[3] Voeten JTM,Bestebroer TM,Nieuwkoop NJ,et al. Antigenic drift in the influenza a virus(H3N2)nucleoprotein and escape from recognition by cytotoxic t lymphocytes[J]. J Virol,2000,74(15):6.
[4]陈忠斌,王升启.抗流感病毒药物的研究进展[J].国际药学研究杂志,1998(2):71-76,800-6807.
[5]国家药典委员会.中华人民共和国药典[M].第四部.北京:中国医药科技出版社,2015:376-377.
[6]谢沐风.如何建立高效液相色谱法测定有关物质的方法[J].中国医药工业杂志,2007,38(1):45-48.
[2] de Jong JC,van Nieuwstadt AP,Kimman TG,et al. Antigenic drift in swine influenza H3 haemagglutinins with implications for vaccination policy[J]. Vaccine,1999,17(12):1321-1328.
[3] Voeten JTM,Bestebroer TM,Nieuwkoop NJ,et al. Antigenic drift in the influenza a virus(H3N2)nucleoprotein and escape from recognition by cytotoxic t lymphocytes[J]. J Virol,2000,74(15):6.
[4]陈忠斌,王升启.抗流感病毒药物的研究进展[J].国际药学研究杂志,1998(2):71-76,800-6807.
[5]国家药典委员会.中华人民共和国药典[M].第四部.北京:中国医药科技出版社,2015:376-377.
[6]谢沐风.如何建立高效液相色谱法测定有关物质的方法[J].中国医药工业杂志,2007,38(1):45-48.