Determination of Phenytoin and Its Intermediates by RP-HPLC with UV-Detection by Timing Wavelength Switching
摘 要
以盐酸酸化的二甲亚砜为溶剂,铁盐催化空气氧化安息香制备苯偶酰,再由苯偶酰与尿素缩合制备苯妥英。在此合成过程中需对反应液中安息香的浓度、中间产物苯偶酰的含量以及最终产物苯妥英的浓度进行检测。试验提出了采用反相高效液相色谱法结合计时波长切换紫外检测法对上述各化合物进行测定。将所需测定的样品溶于乙腈中,所得溶液经0.45 μm滤膜过滤。取滤液(进样量为20 μL)通过kromasil 100-5C18色谱柱(200 mm×4.6 mm,5 μm),以体积比为80:20的乙腈-水溶液作为流动相进行等度洗脱,洗脱液按预设程序进行计时紫外检测。在0~3.0 min和波长218 nm处检测苯妥英;在3.0~4.0 min和波长247 nm处检测安息香;在4.0~6.0 min和波长260 nm处检测苯偶酰。3种化合物标准曲线的线性范围均为0.1~100 mg·L-1,并测得其检出限(3S/N)依次为0.010,0.003 0,0.007 0 mg·L-1。在实际样品基础上加入3个浓度水平的混合标准溶液进行回收试验,测得3种化合物的回收率为95.4%~105%;测定值的相对标准偏差(n=6)为1.8%~4.2%。
Abstract
Benzoin was oxidized by air in the presence of iron salt as catalyst and using dimethyl sulfoxide (acidified with HCl) as solvent to give benzil, which was in turn condensed with urea to give the object product phenytoin. In the course of this synthetic process, it was required to determine phenytoin, the intermediate benzil, and also the starting material benzoin. A method for determination of the 3 compounds mentioned above by RP-HPLC in combination with the UV-detection by timing wavelength switching was tested and proposed. The sample containing the analytes was dissolved with acetonitrile and solution obtained was filtered through 0.45 μm filtering membrane. The filtrate was used for LC analysis. The kromasil 100-5C18 chromatographic column was used as stationary phase, and acetonitrile-H2O solution with the volume ratio of 80:20 was used as mobile phase in isogradient elution. Absorbances (expressed as their peak areas) of the eluates were measured by the programme of timing wavelength switchings as follows:at 0-3.0 min and wavelength of 218 nm (for phenytoin); at 3.0-4.0 min and wavelength of 247 nm (for benzoin); and at 4.0-6.0 min and wavelength of 260 nm (for benzil). Linearity ranges of the standard curves of the 3 compounds were in the same range of 0.1-100 mg·L-1. Detection limits (3S/N) found were 0.010 mg·L-1, 0.003 0 mg·L-1 and 0.007 0 mg·L-1 respectively. Test for recovery was made by addition of mixed standard solutions at 3 concentration levels to matrixes of substantial sample, results of recovery found for the 3 analytes were in the range of 95.4%-105%. Values of RSDs (n=6) were found in the range of 1.8%-4.2%.
中图分类号 O657.7 DOI 10.11973/lhjy-hx202001009
所属栏目 工作简报
基金项目 浙江省分析测试科技计划项目(2018C37046);宁波市公益类科技计划项目(2019C10005);浙江省“生物工程”一流学科项目(ZS2017007);浙江省大学生科技创新(新苗人才计划)项目(2019R420013);国家大学生创新创业训练计划项目(201910876023);浙江万里学院课堂教学改革项目(kg2018014)
收稿日期 2019/5/24
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联系人作者张凯龙(chemnb@163.com)
备注朱爱龄,主要从事食品药品色谱分析
引用该论文: ZHU Ailing,NI Maomao,SONG Yaping,TAN Zhiwen,YU Chao,WANG Caisheng,ZHANG Kailong. Determination of Phenytoin and Its Intermediates by RP-HPLC with UV-Detection by Timing Wavelength Switching[J]. Physical Testing and Chemical Analysis part B:Chemical Analysis, 2020, 56(1): 55~59
朱爱龄,倪貌貌,宋亚萍,谭志文,俞超,汪财生,张凯龙. 反相高效液相色谱法结合计时波长切换紫外检测法测定苯妥英及其中间体的含量[J]. 理化检验-化学分册, 2020, 56(1): 55~59
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【4】JOO C, KANG S, KIM S M, et al. Oxidation of benzoins to benzils using sodium hydride[J]. Tetrahedron Letters, 2010,51(46):6006-6007.
【5】JOSE B, VISHNU UNNI M V, PRATHAPAN S, et al. Oxidation of benzoin to benzil using burgess reagent[J]. Synthetic Communications, 2002,32(16):2495-2498.
【6】倪婉敏,张一平,姜穗媛,等.苯偶酰的绿色催化合成及表征[J].环境化学, 2016,35(5):1035-1041.
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【8】SACHDEV D, NAIK M A, DUBEY A, et al. Environmentally benign aerial oxidation of benzoin over copper containing hydrotalcite[J]. Catalysis Communications, 2010,11(8):684-688.
【9】SHAMIM T, CHOUDHARY D, MAHAJAN S, et al. Covalently anchored metal complexes onto silica as selective catalysts for the liquid phase oxidation of benzoins to benzils with air[J]. Catalysis Communications, 2009,10(14):1931-1935.
【10】毛桂福.HPLC测定人血浆中苯巴比妥、苯妥英、卡马西平浓度[J].中国药学杂志, 2004(7):55-56.
【11】金晨,严丽萍,黄小雅,等.反相高效液相色谱法同时测定新生儿尿液中4种苯丙酮尿症特征酸的含量[J].理化检验-化学分册, 2017,53(1):12-16.
【12】肖丽丽,崇岚,曾国生,等.转换波长高效液相色谱法同时测定复方咪康唑乳中乳酸依沙吖啶、曲安奈德和硝酸咪康唑的含量[J].理化检验-化学分册, 2018,54(12):1415-1418.
【13】刘洁,刘辉,王巨才.RP-HPLC-UV波长切换法测定复方阿司匹林牛磺酸胶囊中咖啡因、阿司匹林及有关物质水杨酸的含量[J].药物分析杂志, 2012,32(11):2068-2070.
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