UPLC法快速测定生脉注射液及其中间体中5-羟甲基糠醛含量
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摘要
目的采用超高效液相色谱技术建立生脉注射液及其中间体中5-羟甲基糠醛的快速限量检查方法。方法样品不经处理直接进样,经ACQUITY UPLC BEH C18色谱柱(2.1 mm×100 mm,1.8μm)分离,柱温35℃。甲醇-水(5∶95)洗脱,流速0.2 mL/min。检测波长284 nm。结果 5-羟甲基糠醛在0.002～0.2 mg/ml范围内线性关系良好,平均回收率为99.49%,RSD值为2.02%。7个厂家的18批生脉注射液中5-羟甲基糠醛含量在0.012～0.083 mg/ml之间,差别较大,同一厂家不同批次的样品测定结果差异不大。麦冬水提醇沉液和五味子水提醇沉液中5-羟甲基糠醛含量远高于红参醇提水沉液和五味子蒸馏液。结论所建方法准确、简便、快速,可为生脉注射液的质量控制和安全评价提供参考。
Objective To establish a rapid limit test method of 5-hydroxymethylfurfural in Shengmai Injection and its intermediates by ultra-performance liquid chromatography(UPLC).Methods The sample was injected directly without preprocessing.The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.8 μm) and the column temperature was set at 35 ℃.The mobile phase was composed of methanol-water(5∶95) at a flaw rate of 0.2 mL/min.The detection wavelength was 284 nm.Results The calibration curve of 5-hydroxymethylfurfural showed good linearity within the range of 0.002～0.2 mg/mL.The average recovery was 99.49% with RSD of 2.02%.Contents of 5-hydroxymethylfurfural in 18 batches of Shengmai Injection from 7 manufactures varied from 0.012 to 0.083 mg/mL.And there were less variations among samples from the same manufacture.Contents of 5-hydroxymethylfurfural in water extraction and alcohol precipitation of Ophiopogonis Radix and water extraction and alcohol precipitation of Schisandrae Chinensis Fructus were much higher than those in alcohol extraction and water precipitation of Ginseng Radix et Rhizoma Rubra and distillate of Schisandrae Chinensis Fructus.Conclusion The proposed method was accurate,simple and rapid,thus providing basis for quality control and safety evaluation of Shengmai Injection.
Objective To establish a rapid limit test method of 5-hydroxymethylfurfural in Shengmai Injection and its intermediates by ultra-performance liquid chromatography(UPLC).Methods The sample was injected directly without preprocessing.The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.8 μm) and the column temperature was set at 35 ℃.The mobile phase was composed of methanol-water(5∶95) at a flaw rate of 0.2 mL/min.The detection wavelength was 284 nm.Results The calibration curve of 5-hydroxymethylfurfural showed good linearity within the range of 0.002～0.2 mg/mL.The average recovery was 99.49% with RSD of 2.02%.Contents of 5-hydroxymethylfurfural in 18 batches of Shengmai Injection from 7 manufactures varied from 0.012 to 0.083 mg/mL.And there were less variations among samples from the same manufacture.Contents of 5-hydroxymethylfurfural in water extraction and alcohol precipitation of Ophiopogonis Radix and water extraction and alcohol precipitation of Schisandrae Chinensis Fructus were much higher than those in alcohol extraction and water precipitation of Ginseng Radix et Rhizoma Rubra and distillate of Schisandrae Chinensis Fructus.Conclusion The proposed method was accurate,simple and rapid,thus providing basis for quality control and safety evaluation of Shengmai Injection.
引文
[1]Cook A P,Macleod T M,Appleton J D,et al. Reversed-phase highperformance liquid chromatographic method for the quantification of 5-hydroxymethylfurfural as the major degradation product of glucose in infusion fluids[J]. J Chromatogr A,1989,467(2):395.
[2]Ulbricht R J,Northup S J,Thomas J A. A review of 5-hydroxymethylfurfural(HMF)in parenteral solutions[J]. Fundam Appl Toxicol,1984,4(5):843.
[3]闫琰,鄢丹,张萍,等.中药注射剂不良反应早期预警方法的研究(I)—安全相关物质5-羟甲基糠醛的研究[J].中华中医药杂志,2010,25(12):2268.
[4]Zhang X M,Chan C C,Stamp D,et al. Initiation and promotion of colonic aberrant crypt foci in rats by 5-hydroxymethyl-2-furaldehyde in thermolyzed sucrose[J]. Carcinogenesis,1993,14(4):773.
[5]Surh YJ,Tannenbaum SR. Activation of the maillard reaction product 5-(hydroxymethyl)furfural to strong mutagens via allylic sulfonation and chlorination[J]. Chem Res Toxicol,1994,7(3):313.
[6]国家药典委员会.中国药典,二部[S].北京:中国医药科技出版社,2015.
[7]周碧青,张素平,张金彪.分光光度法和比色卡法快速测定蜂蜜中羟甲基糠醛[J].分析试验室,2016,35(5):2268.
[8]严赟,罗佚. HPLC法测定血栓通注射液中5-羟甲基糠醛的含量[J].中国民族民间医药,2014,6:31.
[9]程巧鸳,郭增喜,陈碧莲. RP-HPLC法同时测定香丹注射5-羟甲基糠醛和酚酸类成分的含量[J].医药导报,2015,34(1):95.
[10]苏雪清,黄燕萍.舒血宁注射液中5-羟甲基糠醛的含量测定[J].天津药学,2013,25(1):7.
[11]臧清策,何菁菁,白进发,等.快速筛查中药注射液中有害物质5HMF的LC-MS/MS方法及其质量评价研究[J].药学学报,2013,48(11):1705.
[12]聂黎行,何雨晴,戴忠,等.藿香正气水快速质量评价(Ⅰ)-化学计量学辅助的UPLC指纹图谱研究[J].中国药学杂志,2017,52(20):1862.
[13]杨留波,杨烨,王祥培,等.艾纳香药材UPLC指纹图谱鉴别[J].时珍国医国药,2016,27(9):2174.
[14]姜辉,李竹青,秦秀娟,等.疏肝健脾方水提工艺的正交试验法结合UPLC优选[J].时珍国医国药,2016,27(6):1299.
[15]WS3-B-2865-98-2011,国家食品药品监督管理据国家药品标准[S].
[16]潘卓,邵禾欣,刘婷,等.中药注射剂中安全性相关物质5-羟甲基糠醛的研究进展[J].中国中药杂志,2017,42(10):1842.
[17]WS3-B-3267-98-2012,国家食品药品监督管理据国家药品标准[S].
[18]WS3-B-3766-98-2011,国家食品药品监督管理据国家药品标准[S].
[2]Ulbricht R J,Northup S J,Thomas J A. A review of 5-hydroxymethylfurfural(HMF)in parenteral solutions[J]. Fundam Appl Toxicol,1984,4(5):843.
[3]闫琰,鄢丹,张萍,等.中药注射剂不良反应早期预警方法的研究(I)—安全相关物质5-羟甲基糠醛的研究[J].中华中医药杂志,2010,25(12):2268.
[4]Zhang X M,Chan C C,Stamp D,et al. Initiation and promotion of colonic aberrant crypt foci in rats by 5-hydroxymethyl-2-furaldehyde in thermolyzed sucrose[J]. Carcinogenesis,1993,14(4):773.
[5]Surh YJ,Tannenbaum SR. Activation of the maillard reaction product 5-(hydroxymethyl)furfural to strong mutagens via allylic sulfonation and chlorination[J]. Chem Res Toxicol,1994,7(3):313.
[6]国家药典委员会.中国药典,二部[S].北京:中国医药科技出版社,2015.
[7]周碧青,张素平,张金彪.分光光度法和比色卡法快速测定蜂蜜中羟甲基糠醛[J].分析试验室,2016,35(5):2268.
[8]严赟,罗佚. HPLC法测定血栓通注射液中5-羟甲基糠醛的含量[J].中国民族民间医药,2014,6:31.
[9]程巧鸳,郭增喜,陈碧莲. RP-HPLC法同时测定香丹注射5-羟甲基糠醛和酚酸类成分的含量[J].医药导报,2015,34(1):95.
[10]苏雪清,黄燕萍.舒血宁注射液中5-羟甲基糠醛的含量测定[J].天津药学,2013,25(1):7.
[11]臧清策,何菁菁,白进发,等.快速筛查中药注射液中有害物质5HMF的LC-MS/MS方法及其质量评价研究[J].药学学报,2013,48(11):1705.
[12]聂黎行,何雨晴,戴忠,等.藿香正气水快速质量评价(Ⅰ)-化学计量学辅助的UPLC指纹图谱研究[J].中国药学杂志,2017,52(20):1862.
[13]杨留波,杨烨,王祥培,等.艾纳香药材UPLC指纹图谱鉴别[J].时珍国医国药,2016,27(9):2174.
[14]姜辉,李竹青,秦秀娟,等.疏肝健脾方水提工艺的正交试验法结合UPLC优选[J].时珍国医国药,2016,27(6):1299.
[15]WS3-B-2865-98-2011,国家食品药品监督管理据国家药品标准[S].
[16]潘卓,邵禾欣,刘婷,等.中药注射剂中安全性相关物质5-羟甲基糠醛的研究进展[J].中国中药杂志,2017,42(10):1842.
[17]WS3-B-3267-98-2012,国家食品药品监督管理据国家药品标准[S].
[18]WS3-B-3766-98-2011,国家食品药品监督管理据国家药品标准[S].