Development of ultrahigh-throughput NMR spectroscopic analysis utilizing capillary flow NMR technology

被引:6
作者
Bailey, NJC [1 ]
Marshall, IR [1 ]
机构
[1] SCYNEXIS Europe Ltd, Ongar CM5 0GS, Essex, England
关键词
D O I
10.1021/ac0501689
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
An ultrahigh-throughput method for acquiring H-1 NMR spectra is described. By constructing a continuous flow system utilizing an HPLC pump, autosampler, and a capillary flow NMR probe, it was possible to inject samples into the NMR spectrometer every 30 s using a continuous flow rate of 30 mu L/min. H-1 NMR spectroscopic data were acquired continuously into a pseudo-2D data file, with a 96-well-plate completed in < 50 min. Spectra in continuous flow mode were readily obtained from similar to 3.4 mu g (500 MHz), while the LOD was < 850 ng. There was found to be little variation in either sample broadening within the flow system or signal intensities between multiple injections. Ibis system offers several advantages over more conventional NMR spectroscopic analyses, notably the limited solvent required, high sensitivity, high speed, and improved spectral quality as a result of reduced spectral "dead" regions resulting from residual solvent levels.
引用
收藏
页码:3947 / 3953
页数:7
相关论文
共 18 条
[1]   High-throughput method for the production and analysis of large natural product libraries for drug discovery [J].
Eldridge, GR ;
Vervoort, HC ;
Lee, CM ;
Cremin, PA ;
Williams, CT ;
Hart, SM ;
Goering, MG ;
O'Neil-Johnson, M ;
Zeng, L .
ANALYTICAL CHEMISTRY, 2002, 74 (16) :3963-3971
[2]  
Ermer J, 2000, BIOMED CHROMATOGR, V14, P373, DOI 10.1002/1099-0801(200010)14:6<373::AID-BMC29>3.0.CO
[3]  
2-S
[4]   High-throughput 1H NMR and HPLC characterization of a 96-member substituted methylene malonamic acid library [J].
Hamper, BC ;
Snyderman, DM ;
Owen, TJ ;
Scates, AM ;
Owsley, DC ;
Kesselring, AS ;
Chott, RC .
JOURNAL OF COMBINATORIAL CHEMISTRY, 1999, 1 (02) :140-150
[5]   Analysis of multiple samples using multiplex sample NMR: Selective excitation and chemical shift imaging approaches [J].
Hou, T ;
Smith, J ;
MacNamara, E ;
Macnaughtan, M ;
Raftery, D .
ANALYTICAL CHEMISTRY, 2001, 73 (11) :2541-2546
[6]   Hyphenation of capillary separations with nuclear magnetic resonance spectroscopy [J].
Jayawickrama, DA ;
Sweedler, JV .
JOURNAL OF CHROMATOGRAPHY A, 2003, 1000 (1-2) :819-840
[7]   Flow NMR applications in combinatorial chemistry [J].
Keifer, PA .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2003, 7 (03) :388-394
[8]   Hyphenation of capillary HPLC to microcoil 1H NMR spectroscopy for the determination of tocopherol homologues [J].
Krucker, M ;
Lienau, A ;
Putzbach, K ;
Grynbaum, MD ;
Schuger, P ;
Albert, K .
ANALYTICAL CHEMISTRY, 2004, 76 (09) :2623-2628
[9]   Flow injection analysis with multiple on-line spectroscopic analysis (UV, IR, 1H-NMR and MS) [J].
Lenz, E ;
Taylor, S ;
Collins, C ;
Wilson, ID ;
Louden, D ;
Handley, A .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2002, 27 (1-2) :191-200
[10]   Application of flow NMR to an open-access pharmaceutical environment [J].
Leo, GC ;
Krikava, A ;
Caldwell, GW .
ANALYTICAL CHEMISTRY, 2003, 75 (08) :1954-1957