手性NACE法测定酒石酸美托洛尔片剂中对映体的含量
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摘要
目的:建立手性非水毛细管电泳法(NACE法)测定酒石酸美托洛尔片剂中对映体的含量。方法:以D-葡萄糖酸-硼酸络合酸为手性选择剂,在优化过的NACE手性分离条件下展开相关研究。优化的NACE手性分离条件:未涂层熔融石英毛细管(55.0 cm×50μm,有效长度为45.0 cm);背景缓冲液为含8 mmol·L-1 D-葡萄糖酸、120 mmol·L~(-1)硼酸、43.2 mmol·L~(-1)三乙胺的甲醇溶液;10 cm,5 s重力进样;运行电压20 kV;检测波长224 nm;柱温为室温。结果:酒石酸美托洛尔的2个对映体质量浓度在7.5～250.0μg·mL~(-1)范围内,与峰面积呈现良好的线性关系;对映体1的定量下限和检测下限分别为7.5μg·mL~(-1)和2.5μg·mL~(-1);对映体2的定量下限和检测下限分别为25.0μg·mL~(-1)和7.5μg·mL~(-1);对映体1和对映体2的加样回收率分别为99.7%、98.0%、97.2%和97.7%、98.0%、98.0%,均在95.0%～105.0%范围内。6个批次的酒石酸美托洛尔片剂中对映体1和对映体2的标示量百分含量均在96.6%～102.5%之间。结论:该方法经验证可用于酒石酸美托洛尔片剂中对映体含量的测定。
Objective:To establish a method for the determination of enantiomers of metoprolol tartrate in tablets by nonaqueous capillary electrophoresis(NACE).Methods:D-Gluconic acid-boric acid complex was used as the chiral selector.The experiments were carried out under the optimized chiral NACE conditions.The optimized conditions were as follows:Enantiomeric sepraration was performed in an unmodified fused silica capillary of 50.0 μm with 55.0 cm of total length and 45.0 cm of effective length;the running buffer solution was a mixture of 8 mmol·L~(-1) D-gluconic acid,120 mmol·L~(-1) boric acid and 43.2 mmol·L~(-1) triethylamine in methanol;injection were performed hydrostatically for 5 s at a 10 cm height difference;the applied voltage was 20 kV;the detection wavelength was 224 nm;the experiments were performed at room temperature.Results:Good linearity for the two enantiomers of metoprolol tartrate were obtained in the range of 7.5-250.0 μg·mL~(-1).The limit of quantification(LOQ)and the limit of detection(LOD)for enantiomer 1 were 7.5 μg·mL~(-1) and 2.5 μg·mL~(-1),respectively,and for enantiomer 2,25.0 μg·mL~(-1) and 7.5 μg·mL~(-1),respectively. The recoveries for each enantiomer were 99.7%,98.0%,97.2% and 97.7%,98.0%,98.0%,respectively,with all in the range of 95.0%-105.0%.The contents of enantiomer 1 and enantiomer 2 in six batches of metoprolol tartrate tablets were all in the ranges of 96.6%-102.5%.Conclusion:The method validated by methodology is suitable for the determination of enantiomer contents in metoprolol tartrate tablets.
Objective:To establish a method for the determination of enantiomers of metoprolol tartrate in tablets by nonaqueous capillary electrophoresis(NACE).Methods:D-Gluconic acid-boric acid complex was used as the chiral selector.The experiments were carried out under the optimized chiral NACE conditions.The optimized conditions were as follows:Enantiomeric sepraration was performed in an unmodified fused silica capillary of 50.0 μm with 55.0 cm of total length and 45.0 cm of effective length;the running buffer solution was a mixture of 8 mmol·L~(-1) D-gluconic acid,120 mmol·L~(-1) boric acid and 43.2 mmol·L~(-1) triethylamine in methanol;injection were performed hydrostatically for 5 s at a 10 cm height difference;the applied voltage was 20 kV;the detection wavelength was 224 nm;the experiments were performed at room temperature.Results:Good linearity for the two enantiomers of metoprolol tartrate were obtained in the range of 7.5-250.0 μg·mL~(-1).The limit of quantification(LOQ)and the limit of detection(LOD)for enantiomer 1 were 7.5 μg·mL~(-1) and 2.5 μg·mL~(-1),respectively,and for enantiomer 2,25.0 μg·mL~(-1) and 7.5 μg·mL~(-1),respectively. The recoveries for each enantiomer were 99.7%,98.0%,97.2% and 97.7%,98.0%,98.0%,respectively,with all in the range of 95.0%-105.0%.The contents of enantiomer 1 and enantiomer 2 in six batches of metoprolol tartrate tablets were all in the ranges of 96.6%-102.5%.Conclusion:The method validated by methodology is suitable for the determination of enantiomer contents in metoprolol tartrate tablets.
引文
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[2]车艳,沈春健.酒石酸美托洛尔对心脏瓣膜病伴心力衰竭患者的影响研究[J].中国医学创新,2017,14(2):5CHE Y,SHEN CJ.Impact study of tartaric acid metoprolol in patients with valvular heart disease and heart failure[J].Med Innov China,2017,14(2):5
[3]狄潘潘,徐自奥,李家明,等.美托洛尔及其手性对映体的合成工艺研究最新进展[J].安徽化工,2015,41(1):12DI PP,XU ZA,LI JM,et al.Recent progress of the metoprolol and chiral enantiomers synthesis[J].Anhui Chem Ind,2015,41(1):12
[4]DASBISWAS A,SHINDE S,DASBISWAS D.S-metoprolol:the2008 clinical review[J].J Ind Med Assoc,2008,106(4):259
[5]程彪平,李来生,周仁丹,等.β-环糊精类手性液相色谱固定相拆分和测定药片中美托洛尔对映体[J].分析试验室,2014,33(10):1151CHENG BP,LI LS,ZHOU RD,et al.Separation and determination of metoprolol enantiomers in tablets byβ-cyclodextrin chiral liquid chromatography stationary phase[J].Chin J Anal Lab,2014,33(10):1151
[6]徐秀珠,邹莉,胡明华,等.离子对色谱法分离氨基醇类对映体[J].分析化学,2001,29(11):1295XU XZ,ZOU L,HU MH,et al.Separation of alcohol enantiomers by ion-pair chromatography[J].Chin J Anal Chem,2001,29(11):1295
[7]杨娟,王利娟,郭巧玲,等.以L-酒石酸正己酯-硼酸配合物作为反相液相色谱手性流动相添加剂拆分5种β-受体阻滞剂[J].色谱,2012,30(3):280YANG J,WANG LJ,GUO QL,et al.Chiral separation of fiveβ-blockers using di-n-hexyl L-tartrate-boric acid complex as mobile phase additive by reversed-phase liquid chromatography[J].Chin J Chromatogr,2012,30(3):28
[8]ZOU YN,WANG LJ,LIU Q,et al.Enantioseparations of 11 amino alcohols using di-n-amyl L-tartrate–boric acid complex as chiral mobile phase additive by RP-HPLC[J].Chromatographia,2015,78(11-12):753
[9]HOUJY,LIG,WEIYQ,etal.Analysisoffivealkaloids using surfactant-coated multi-walled carbon nanotubes as the pseudostationary phase in nonaqueous capillary electrophoresis[J].J Chromatogr A,2014,1343(5):174
[10]LV LL,WANG LJ,ZOU YN,et al.Chiral separation by nonaqueous capillary electrophoresis using L-sorbose–boric acid complexes as chiral ion-pair selectors[J].RSC Adv,2016,6(106):104193
[11]AN N,WANG LJ,ZHAO JJ,et al.Enantioseparation of fourteen amino alcohols by nonaqueous capillary electrophoresis using lactobionic acid D-(+)-xylose–boric acid complexes as chiral selectors[J].Anal Methods,2016,8(5):1127
[12]GOMG ZS,DUAN LP,TANG AN.Amino-functionalized silica nanoparticles for improved enantiomeric separation in capillary electrophoresis using carboxymethyl-β-cyclodextrin(CM-β-CD)as a chiral selector[J].Microchim Acta,2015,182(7-8):1297