稳定同位素标记物D_3-左氧氟沙星的合成及表征
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摘要
以市售的左氧氟沙星羧酸为原料,以氘代甲醇为稳定同位素标记物前体,经无水哌嗪取代、双氘代甲基化、氢氧化钠水解合成出稳定同位素标记的D_3-左氧氟沙星,3步反应总收率为45.5%。目标产物经MS、~1HNMR表征确认,通过高效液相色谱确认化学纯度>98%,经计算同位素丰度为97.7%。该合成路线具有操作简便、试剂廉价等优点。
Stabilized isotope-labeled D_3-levofloxacin was synthesized by using commercially available levofloxacin carboxylic acid as starting material and deuterated methanol as a stable isotope-labeled precursor with three steps.The steps are in order of replacing with anhydrous piperazine,bis-deuterated methylation and hydrolized by sodium hydroxide with totally yield of 45. 5%. The target product was confirmed by MS,~1HNMR and HPLC. The chemical purity was higher than 98% and the isotope abundance was 97. 7% by calculation.Designed synthetic route is simple and commercial.
Stabilized isotope-labeled D_3-levofloxacin was synthesized by using commercially available levofloxacin carboxylic acid as starting material and deuterated methanol as a stable isotope-labeled precursor with three steps.The steps are in order of replacing with anhydrous piperazine,bis-deuterated methylation and hydrolized by sodium hydroxide with totally yield of 45. 5%. The target product was confirmed by MS,~1HNMR and HPLC. The chemical purity was higher than 98% and the isotope abundance was 97. 7% by calculation.Designed synthetic route is simple and commercial.
引文
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[2]熊攀,李振华,钟为慧.左氧氟沙星合成研究进展[J].浙江化工,2014,45(9):5-8.
[3]毕海林,唐建华,唐达.左旋氧氟沙星药动学-药效学研究进展[J].黑龙江畜牧兽医科技版,2014,17:52-54.
[4]程雨豪.一例左氧氟沙星致喉头水肿的急救处理[J].当代护士:学术版(中旬刊),2016,4(2):148-149.
[5]孙忠,石文伟,董佃良,等.左氧氟沙星的不良反应[J].中国医药指南,2012,12:458-459.
[6]刘金虹,关宗.左氧氟沙星新剂型研制[J].中国医院医学杂志,2006,18(3):57-59.
[7]袁堃,王薇薇,刘璐,等.左氧氟沙星眼用制剂研究进展[J].武警医学院学报,2008,17(11):1 034-1 036.
[8]李聪,程雪峰,顾健,等.左氧氟沙星热敏性凝胶制备及局部治疗大鼠化脓性中耳炎的研究[J].中国眼耳鼻喉科杂志,2013,13(6):372-375.
[9]姚宏,王辉,苏佳亮,等.某饮用水处理厂中5种抗生素的去除[J].环境工程学报,2013,7(3):801-809.
[10]侯霞,董学畅,杨光宇,等.快速分离柱HPLC测定猪肉中氟喹诺酮类兽药的残留[J].云南民族大学学报:自然科学版,2007,16(3):225-227.
[11]王琦,黄伟,梁熙,等.HPLC法检测兔胫骨及骨髓中的左氧氟沙星[J].重庆医科大学学报,2016,41(2):146-150.
[12]AGUILAR-CARRASCO J C.Rapid and sensitive determination of levofloxacin in microsamples of human plasma by high-performance liquid chromatography and its application in a pharmacokinetic study[J].Biomed.Chromatogr.,2015,29(3):341-345.
[13]WEI Hong,HU Da,LI Ke-bin,et al.Intensification of levofloxacin sono-degradation in a US/H2O2system with Fe3O4magnetic nanoparticles[J].Chin.J.Chem.Eng.,2015,23(1):296-302.
[14]LEE S J.Development and validation of LC-ESI-MS/MS method for analysis of moxifloxacin and levofloxacin in serum of multidrug-resistant tuberculosis patients:potential application as therapeutic drug monitoring tool in medical diagnosis[J].J.Chromatogr.B,2016,1 009/1 010:138-143.
[15]欧阳玥,孙晓红,闫静,等.稳定同位素标记技术在生物分子相对定量分析研究中的应用与进展[J].科学通报,2013,58(27):2 762-2 778.
[16]郭常川,曾苏.药物分析几种新技术的应用进展[J].浙江大学学报:医学版,2011,40(1):1-6.
[17]美国药典委员会.USP36-NF31[M].美国食品药品监督管理局,2012:4 099-4 101.
[18]蔡银萍,雷雯,郑波,等.稳定同位素氘标记苏丹红Ⅰ的同位素丰度和化学纯度分析[J].同位素,2014,27(2):65-71.