~(19)F qNMR在含氟制剂含量测定中的应用
|
摘要
目的:建立~(19)F核磁共振定量(qNMR)测定片剂中含氟药物含量的方法。方法:以4,4′-二氟二苯甲酮为内标,氘代DMSO为溶剂,采用反门控去耦的zgfhigqn.2脉冲序列,利用~(19)F qNMR测定卡格列净片中卡格列净含量。试验参数如下:谱宽SW=40×10-6,射频中心频率O1P=-110×10-6,采样点数TD=128 k,采样时间AQ=3.5 s,弛豫延迟时间D1=20 s,扫描次数32次。结果:通过简单的过滤或离心处理后,使用~(19)F qNMR测得6片卡格列净片中卡格列净含量分别为98.2%、98.9%、101.0%、99.7%、99.2%,与HPLC外标法测定结果相近。结论:~(19)F qNMR可以用于含氟药物制剂中药品含量测定,这种技术前处理简单,检测速度快,不受辅料等干扰,可以用于含氟药物制剂含量的高通量测定。
Objective:To establish a ~(19)F quantitative nuclear magnetic resonance(q NMR) method to determine the content of active pharmaceutical ingredient(API) in fluorine-containing preparation. Methods:In ~(19)F qNMR experiments,4,4 ′-difluorobenzophenone was used as an internal standard. DMSO-d6 was used as solvent and zgfhigqn-.2 pulse sequence w6 ith inverse gated decoupling was applied. Other parameters were as follows:SW=40×106,O1 P=-110×10-,TD=128 k,AQ=3.5 s,D1=20 s and NS=32. Results:After simple pre-treatment of filtration or centrifuge,the content of canagliflozin in 5 tablets were measured using ~(19)-qNMR. The results were 98.2%,98.9%,101.0%,99.7% and 99.2%,respectively. The results were similar to those from HPLC method. Conclusion:~(19)F qNMR can be used in determining the contents of fluorine-containing APIs in tablets. This method only requires minimal pre-treatment and its testing speed is rapid. Meanwhile,the excipients have no interference with the determination. This technology is suitable for high-throughput measuring the API content in fluorine-containing preparation.
Objective:To establish a ~(19)F quantitative nuclear magnetic resonance(q NMR) method to determine the content of active pharmaceutical ingredient(API) in fluorine-containing preparation. Methods:In ~(19)F qNMR experiments,4,4 ′-difluorobenzophenone was used as an internal standard. DMSO-d6 was used as solvent and zgfhigqn-.2 pulse sequence w6 ith inverse gated decoupling was applied. Other parameters were as follows:SW=40×106,O1 P=-110×10-,TD=128 k,AQ=3.5 s,D1=20 s and NS=32. Results:After simple pre-treatment of filtration or centrifuge,the content of canagliflozin in 5 tablets were measured using ~(19)-qNMR. The results were 98.2%,98.9%,101.0%,99.7% and 99.2%,respectively. The results were similar to those from HPLC method. Conclusion:~(19)F qNMR can be used in determining the contents of fluorine-containing APIs in tablets. This method only requires minimal pre-treatment and its testing speed is rapid. Meanwhile,the excipients have no interference with the determination. This technology is suitable for high-throughput measuring the API content in fluorine-containing preparation.
引文
[1]中华人民共和国药典2015年版.四部[S].2015:441Ch P 2015.VolⅣ[S].2015:441
[2]USP 40-NF 35[S].2017:761
[3]BP 2017[S].2017:Appendix II C
[4]EP 9.0[S].2017:2.2.33
[5]HOLZGRABE U.Quantitative NMR spectroscopy in pharmaceutical applications[J].Prog Nucl Magn Reson Spectrosc,2010,57(2):229
[6]张芬芬,蒋孟虹,沈文斌,等.定量核磁共振(QNMR)技术及其在药学领域的应用进展[J].南京师范大学学报,2014,14(2):8ZHANG FF,JIANG MH,SHEN WB,et al.Progress in quantitative nuclear magnetic resonance technology in pharmaceutical applications[J].J Nanjing Norm Univ,2014,14(2):8
[7]张才煜,吴建敏,李憬,等.核磁共振法定量测定氢溴酸东莨菪碱的绝对含量[J].药物分析杂志,2012,32(2):327ZHANG CY,WU JM,LI J,et al.,Quantitative nuclear magnetic resonance determination of the absolute content of scopolamine hydrobromide[J].Chin J Pharm Anal,2012,32(2):327
[8]LIU Y,LIU ZX,LIN L,et al.Direct comparison of 19F q NMR and1H q NMR by characterizing atorvastatin calcium content[J/OL].JAnal Methods Chem,2016,7627823/1-5[2016-08-09].https://www.hindawi.com/journals/jamc/2016/7627823/
[9]刘阳,魏宁漪,岳瑞齐,等.新型19F核磁共振定量技术测定氟哌利多含量[J].中国新药杂志,2014,23(16):1960LIU Y,WEI NY,YUE RQ,et al.Application of novel 19Fquantitative NMR(19F-q NMR)in assay of droperidol[J].Chin JNew Drugs,2014,23(16):1960
[10]刘阳,魏宁漪,张琪,等.19F核磁共振定量技术测定酒石酸吉米格列汀倍半水合物含量[J].药物分析杂志,2014,34(7):1197LIU Y,WEI NY,ZHANG Q,et al.Quantitative analysis of gemigliptin tartrate sesquihydrate by 19F quantitative NMR(19F-q NMR)[J].Chin J Pharm Anal,2014,34(7):1197
[11]PAULI GF,GODECKE T,dc JAKI BU,et al.,Quantitative1H-NMR development and potential of an analytical method:an update[J].J Nat Prod,2012,75(4):834
[12]于小波,沈文斌,相秉仁.定量核磁共振技术及其在药学领域中的应用进展[J].药学进展,2010,34(1):17YU XB,SHEN WB,XIANG BR.Advances in application of quantitative nuclear magnetic resonance technique in pharmaceutical field[J].Prog Pharma Sci,2010,34(1):17
[13]刘英,胡昌勤,核磁共振在抗生素药物定量分析中的应用[J].药物分析杂志,2001,21(6):447LIU Y,HU CQ.Application of NMR in quantitative analysis of antibiotics[J].Chin J Pharm Anal,2001,21(6):447
[14]DIXON AM,LARIVE CK.Modified pulsed-field gradient NMRexperiments for improved selectivity in the measurement of diffusion coefficients in complex mixtures:application to the analysis of the Suwannee River fulvic acid[J].Anal Chem,1997,69(11):2122
[15]PAULI GF,JAKI BU,LANKIN DC.Quantitative 1H NMR:development and potential of a method for natural products analysis[J].J Nat Prod,2005,68(1):133
[2]USP 40-NF 35[S].2017:761
[3]BP 2017[S].2017:Appendix II C
[4]EP 9.0[S].2017:2.2.33
[5]HOLZGRABE U.Quantitative NMR spectroscopy in pharmaceutical applications[J].Prog Nucl Magn Reson Spectrosc,2010,57(2):229
[6]张芬芬,蒋孟虹,沈文斌,等.定量核磁共振(QNMR)技术及其在药学领域的应用进展[J].南京师范大学学报,2014,14(2):8ZHANG FF,JIANG MH,SHEN WB,et al.Progress in quantitative nuclear magnetic resonance technology in pharmaceutical applications[J].J Nanjing Norm Univ,2014,14(2):8
[7]张才煜,吴建敏,李憬,等.核磁共振法定量测定氢溴酸东莨菪碱的绝对含量[J].药物分析杂志,2012,32(2):327ZHANG CY,WU JM,LI J,et al.,Quantitative nuclear magnetic resonance determination of the absolute content of scopolamine hydrobromide[J].Chin J Pharm Anal,2012,32(2):327
[8]LIU Y,LIU ZX,LIN L,et al.Direct comparison of 19F q NMR and1H q NMR by characterizing atorvastatin calcium content[J/OL].JAnal Methods Chem,2016,7627823/1-5[2016-08-09].https://www.hindawi.com/journals/jamc/2016/7627823/
[9]刘阳,魏宁漪,岳瑞齐,等.新型19F核磁共振定量技术测定氟哌利多含量[J].中国新药杂志,2014,23(16):1960LIU Y,WEI NY,YUE RQ,et al.Application of novel 19Fquantitative NMR(19F-q NMR)in assay of droperidol[J].Chin JNew Drugs,2014,23(16):1960
[10]刘阳,魏宁漪,张琪,等.19F核磁共振定量技术测定酒石酸吉米格列汀倍半水合物含量[J].药物分析杂志,2014,34(7):1197LIU Y,WEI NY,ZHANG Q,et al.Quantitative analysis of gemigliptin tartrate sesquihydrate by 19F quantitative NMR(19F-q NMR)[J].Chin J Pharm Anal,2014,34(7):1197
[11]PAULI GF,GODECKE T,dc JAKI BU,et al.,Quantitative1H-NMR development and potential of an analytical method:an update[J].J Nat Prod,2012,75(4):834
[12]于小波,沈文斌,相秉仁.定量核磁共振技术及其在药学领域中的应用进展[J].药学进展,2010,34(1):17YU XB,SHEN WB,XIANG BR.Advances in application of quantitative nuclear magnetic resonance technique in pharmaceutical field[J].Prog Pharma Sci,2010,34(1):17
[13]刘英,胡昌勤,核磁共振在抗生素药物定量分析中的应用[J].药物分析杂志,2001,21(6):447LIU Y,HU CQ.Application of NMR in quantitative analysis of antibiotics[J].Chin J Pharm Anal,2001,21(6):447
[14]DIXON AM,LARIVE CK.Modified pulsed-field gradient NMRexperiments for improved selectivity in the measurement of diffusion coefficients in complex mixtures:application to the analysis of the Suwannee River fulvic acid[J].Anal Chem,1997,69(11):2122
[15]PAULI GF,JAKI BU,LANKIN DC.Quantitative 1H NMR:development and potential of a method for natural products analysis[J].J Nat Prod,2005,68(1):133