Pauli G.F.; Jaki B.; Lankin D. A Routine Experimental Protocol for qHNMR Illustrated with Taxol. Journal of Natural Products 2007, 70(4), in press (http://dx.doi.org/10.1021/np060535).
Abstract: [coming up]
Pauli G.F.; Jaki B.; Lankin D. Quantitative 1H NMR: Development and Potential of a Method for Natural Products Analysis. Journal of Natural Products 2005, 68(1), 133-149 (http://dx.doi.org/10.1021/np0497301).
Abstract: Based on a brief revision of what constitutes state-of-the-art “quantitative experimental conditions” for 1H quantitative NMR (qHNMR), this comprehensive review contains almost 200 references and covers the literature since 1982 with emphasis on natural products. It provides an overview of the background and applications of qHNMR in natural products research, new methods such as decoupling and hyphenation, analytical potential and limitations, and compiles information on reference materials used for and studied by qHNMR. The dual status of natural products, being single chemical entities and valuable biologically active agents that need to be purified from complex matrices, results in an increased analytical demand when testing their deviation from the singleton composition ideal. The outcome and versatility of reported applications lead to the conclusion that qHNMR is currently the principal analytical method to meet this demand. Considering both 1D and 2D 1H NMR experiments, qHNMR has proved to be highly suitable for the simultaneous selective recognition and quantitative determination of metabolites in complex biological matrices. This is manifested by the prior publication of over 80 reports on applications involving the quantitation of single natural products in plant extracts, dietary materials, and materials representing different metabolic stages of (micro)organisms. In summary, qHNMR has great potential as an analytical tool in both the discovery of new bioactive natural products as well as the field of metabolome analysis.
Pauli G.F.; Jaki B.; Lankin D.; Burton, I.; Walter, J. Quantitative NMR (qNMR) of Bioactive Natural Products in Bioactive Natural Products: Detection, Isolation and Structural Determination, 2nd Edition, Colegate, S; Molyneux, R (Eds.), CRC Press [publication scheduled II/2007]
Abstract: [coming up]
Pauli G.F. qNMR - A versatile concept for the validation of natural product reference compounds. Phytochem. Anal. 2001, 12(1), 28-42.
Jaki B.; Sticher O.; Veit M.; Fröhlich R.; Pauli G.F. Evaluation of Glucoiberin Reference Material from Iberis amara by Spectroscopic Fingerprinting. J. Nat. Prod. 2002, 65(4), 517-522.
Wittig J.; Leipolz I.; Graefe E.U.; Jaki B.; Treutter D.; Veit M. Quantification of procyanidins in oral herbal medicinal products containing extracts of Crataegus species. Arzneimittelforschung 2002, 52(2), 89-96.
Saito, T.; Nakaie, S.; Kinoshita, M.; Ihara, T.; Kinugasa, S.; Nomura, A.; Maeda, T. Practical guide for accurate quantitative solution state NMR analysis. Metrologia 2004, 41, 213-218.
Saed Al Deen T.; Brynn Hibbert D.; Hook J.M.; Wells R.J. Quantitative nuclear magnetic resonance spectrometry - II. Purity of phosphorus-based agrochemicals glyphosate (N-(phosphonomethyl)-glycine) and profenofos (O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate) measured by 1H and 31P QNMR spectrometry. Analytica Chimica Acta 2002, 474(1), 125-135.
Wells, R.; Cheung, J.; Hook, J. M. Dimethylsulfone as a universal standard for analysis of organics by QNMR. Accred. Qual. Assur. 2004, 9, 450-456.
Pinciroli, V.; Biancardi, R.; Visentin, G.; Rizzo, V. The Well-Characterized Synthetic Molecule: A Role for Quantitative 1H NMR. Org. Proc. Res. Devel. 2004, 8, 381-384.
Burton, I. W.; Quilliam, M. A.; Walter, J. A. Quantitative 1H NMR with external standards: use in preparation of calibration solutions for algal toxins and other natural products. Anal. Chem. 2005, 77, 3123-3131.
Hays, P. A. Proton nuclear magnetic resonance spectroscopy (NMR) methods for determining the purity of reference drug standards and illicit forensic drug seizures. J. Forensic Sci. 2005, 50, 1342-1360.
Rizzo, V.; Pinciroli, V. Quantitative NMR in synthetic and combinatorial chemistry. J. Pharm. Biomed. Anal. 2005, 38, 851-857.
Dumas, M.-E.; Maibaum, E. C.; Teague, C.; Ueshima, H.; Zhou, B.; Lindon, J. C.; Nicholson, J. K.; Stamler, J.; Elliott, P.; Chan, Q.; Holmes, E. Assessment of Analytical Reproducibility of 1H NMR Spectroscopy Based Metabonomics for Large-Scale Epidemiological Research: the INTERMAP Study. Anal. Chem. 2006, 78, 2199-2208.
Shao, G.; Kautz, R.; Peng, S.; Cui, G.; Giese, R. W. Calibration by NMR for quantitative analysis: p-Toluenesulfonic acid as a reference substance. Journal of Chromatography, A 2007, 1138, 305-308.
Ala-Korpela, M.; Lankinen, N.; Salminen, A.; Suna, T.; Soininen, P.; Laatikainen, R.; Ingman, P.; Jauhiainen, M.; Taskinen, M.-R.; Heberger, K.; Kaski, K. The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent. Atherosclerosis (Amsterdam, Netherlands) 2007, 190, 352-358.
Manetti C.; Bianchetti C.; Bizzarri M.; Casciani L.; Castro C.; D'Ascenzo G.; Delfini M.; Di Cocco M.E.; Lagana A.; Miccheli A.; Motto M.; Conti F. NMR-based metabonomic study of transgenic maize. Phytochemistry 2004, 65(24), 3187-3198.
Fernandez-Ramirez A.; de la Luz Salazar-Cavazos M.; Rivas-Galindo V.; Ceniceros-Almaguer L.; de Torres N.W. Determination of isoperoxisomicine A1 content in peroxisomicine A1 batches by 1H NMR. Anal. Lett. 2004, 37(12), 2433-2444.
Wells R.; Cheung J.; Hook J.M. Dimethylsulfone as a universal standard for analysis of organics by QNMR. Accred. Qual. Assur. 2004, 9(8), 450-456.
Jaki, B.; Franzblau, S. G.; Pauli, G. F. Phytochem. Anal. 2004, 15, 213-219.
Malz, F. Quantitative NMR-Spektroskopie als Referenzverfahren in der analytischen Chemie; Ph.D. Dissertation, Humboldt-Universität Berlin: Berlin, 2003, 147 pp.
Deubner, Ralph. Quantitative NMR-Spektroskopie zur Reinheitsbestimmung von Arzneistoffen; Ph.D. Dissertation, University of Wuerzburg: Wuerzburg, 2004 [pdf]
Abstract: Quantitative analysis It could be shown on the basis of different substances that the NMR spectroscopy is able to quantify impurities of pharmaceuticals. For the quantification of impurities of the antidepressive drug fluvoxamine the pharmacopoeia describes an ion-pair chromatographic method. Since the antidepressive activity resides on the E-isomer the content of the Z-isomer has to be lim-ited. Since ion-pair chromatography often lacks of robustness, qNMR is an alternative. The quantitative evaluation of 1H NMR spectra of a mixture of the two isomers is possible without extensive sample preparation. The signals of the hydrogens at position 2 of both isomers are well separated in the spectrum. If these are quantitative evaluated, under optimized conditions, e.g. with respect to T1-relaxation time, it is possible to limit the content of the Z-isomer to 0.2%. For analysis of degradation products of perphenazine enantate qNMR is a suitable method. Perphenazine enantate can be cleaved by ester hydrolysis. Using the integral area of the signal of the hydrogens at position 21 of per-phenazine in comparison to the integral area of the overlapping signals of the hydrogens at position 11 of both substances perphenazine and perphenazine enantate it was possible to quantify perphenazine as a degradation product of perphenazine as well perphenazine enantate in perphenazine. Additionally the area of the aromatic hydrogens can be used for the analysis of the oxidation. The oxidation of the sulfur of the the phenothiazine moiety to the sulfoxide and the sulfone changes the chemical shifts of the corresponding hydrogens. This enables a half-quantitative assessment. Finally it was possible to quantify the two epimers quinine and quinidine as an impurity in either drug. Again signals of both substances could be identified to be used for quantification. In both cases quinine as impurity of quinidine and vice versa the impurity can be limited to 2.5 per cent as required by the pharmacopeias. Gentamicin sulfate 1H-NMR spectroscopy was also used as an analytical method to characterize the composition of gentamicin. Gentamicin is produced from Micromonospora purpurea by fermentation and consists of different main and side components. The composition varies when applying different fermentation conditions. A number of deaths in connection with the application of the antibiotic drug gentamicin in the USA were reported. Different impurities were suspected to be responsible for these deaths. In the current pharmacopoeia monograph an HPLC method is described which is able to quantify all main components but does not separate all side components. In addition, the total elution time is long. Thus late eluting substances show very broad peaks. Furthermore the used pulsed amperometric detector is very sensitive and the method is not very robust over all. Using one- and two-dimensional routine NMR techniques and selective TOCSY experiments it was possible to assign all signals in the 1H- and 13C-NMR spectra of all main and side components. The area of the anomeric hydrogens is appropriate to evaluate the purity of gentamicin and the proportions between the main components. In the part of the 400 MHz 1H-NMR spectrum integration of the H20 signals of the main components is impossible due to the missing baseline separation. However, using 600 MHz spectra integration is possible. In this way the proportions between the main components can be determined. The results achieved in this way show good accordance to the results obtained with an MEKC separation. More than 40 gentamicin samples from different manufactures were studied, com-pared and divided into several groups, based on their impurity profile. As a lead impurity sisimocin has been identified. Besides that, the comparison of the impurity profiles enables to trace the trade ways. Some of the samples which led to the deaths were among the samples being classified in the impure groups.
Forshed, Jenny. Processing and analysis of NMR data: Impurity determination and metabolic profiling; Ph.D. Dissertation, Stockholm University, Department of Analytical Chemistry, 2005, [pdf]
Abstract: This thesis describes the use of nuclear magnetic resonance (NMR) spectrometry as an analytical tool. The theory of NMR spectroscopy in general and quantitative NMR spectrometry (qNMR) in particular is described and the instrumental properties and parameter setups for qNMR measurements are discussed. Examples of qNMR are presented by impurity determination of pharmaceutical compounds and analysis of urine samples from rats fed with either water or a drug (metabolic profiling). The instrumental parameter setup of qNMR and traditional data pre-treatments are examined. Spectral smoothing by convolution with a triangular function, which is an unusual application in this context, was shown to be successful regarding the sensitivity and robustness of the method in paper II. In addition, papers III and IV comprise the field of peak alignment, especially designed for 1H-NMR spectra of urine samples. This is an important preprocessing tool when multivariate analysis is to be applied. A novel peak alignment method was developed and compared to the traditional bucketing approach and a conceptually different alignment method. Univariate, multivariate, linear and nonlinear data analyses were applied to qNMR data. In papers I–II, calibration models were created to examine the potential of qNMR for these applications. The data analysis in papers III–VI was mainly explorative. The potential of data fusion and data correlation was examined in order to increase the possibilities of analysing the highly complex samples from metabolic profiling (papers V–VI). Data from LC/MS analysis of the same samples were used with the 1H-NMR data in different ways. Correlation analyses between the 1H-NMR data and the drug metabolites identified from the LC/MS data were also performed. In this process, data fusion proved to be a valuable tool.
http://pubs.acs.org/subscribe/journals/mdd/v07/i02/pdf/204feature_yan.pdf