Quantitative Online NMR Spectroscopy of Technical Mixtures: On the Fly Quantification of Fluids
In this paper quantitative NMR spectroscopy is demonstrated as a tool for process analytical technology (PAT) in order to obtain real time information from dynamic processes. Different methods for quantification are presented and as a result the limit of detection for NMR measurement could be determined to 3.3 mg kg−1 (ethanol in water). As model processes esterification reactions and dissolution of pharmaceutical formulations are presented and important process parameters are extracted. Furthermore it is demonstrated that not only 1H-NMR spectroscopy can be used for process monitoring but also 13C-NMR for technical mixtures.
KeywordsNMR Quantification Online Process analytical technology
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The authors kindly thank Bastian Bräuer for sample preparation (methanol in biodiesel), Hugo Ent (VSL) for the kind supply of biodiesel and Andrea Paul for proof reading. We also thank DFG for financial support.
- 1.Malz F, Jancke H (2005) Validation of quantitative NMR. J Pharm Biomed Anal 38: 813–823Google Scholar
- 2.Bayer E, Albert K, Nieder M, Gromm E, Keller T (1979) On-line coupling of high-performance liquid chromatography and nuclear magnetic resonance. J Chromatogr 186: 497–507Google Scholar
- 3.Maiwald M, Fischer HH, Kim Y-K, Albert K, Hasse H (2004) quantitative High-resolution on-line NMR spectroscopy in reaction and process monitoring. J of Magnet Reson 166: 135–146Google Scholar
- 4.Akoka S, Barantin L, Trierweiler M (1999) Anal Chem 71:2554–2557Google Scholar
- 5.Harris RK (1976) N.m.r. and the periodic table. Chem Soc Rev 5: 1–22Google Scholar
- 6.Klein S (2012) Anwendung und Vergleich unterschiedlicher Dissolutionsmethoden. TechnoPharm 2: 54–61Google Scholar
- 7.Costa P, Sousa Lobo JM (2001) Modelling and comparison of dissolution profiles. Eur J Pharma Sci 13:123–133Google Scholar