Improved solid-state NMR quantifications of active principles in pharmaceutical formulations

A method for improved quantification of 1H NMR signals under low-resolution conditions for solids

“…Under typical conditions the sensitivity of the NMR experiment is rather limited which does not make NMR a likely candidate for trace analysis where the analyte is below 1% in concentration. Applications of solid-state qNMR are wide spread too, covering different areas as, for example pharmaceutical formulation [3,4], cement base materials [5,6], drugs [7][8][9], coals [10] or amorphous materials [11] and different nuclei like 13 C [3,9,[12][13][14], 29 Si [13], 119 Sn [13] and 23 Na [15]. Interestingly methods based on 13 C-CP-MAS NMR have proved to be quantifiable for organic matter [13].…”

“…Systematic studies in solid-state qNMR have highlighted different sources of errors, for example repetition delays (related to spin-lattice relaxation) [3,9], pulse-length effects [9], spectrometer stability issues [15], sample preparation, quantitative analysis with internal or external reference [2,3,14,15] and packing effects of the material in the MAS rotor [14,15], which lead to false intensities when excited by inhomogeneous radio-frequency fields. An exhaustive protocol for solid-state qNMR has recently been published [9].…”

Multiple-Quantum NMR Studies on Molecular Mixtures

“…Although quantitative NMR is so developed that it can be considered as a field on its own, the vast majority concerns 1D 1 H spectroscopy [39,40]. In fact, the introduction of common 2D experiments as tools for quantitation of mixtures has been delayed by issues such as the duration of the experiment .…”

Sampling Methods for Quantification of Solid-state Phases in Powder Samples with Solid-state NMR Spectroscopy

“…[1][2][3][4][5][6][7][8][9][10][11] For example, the polymorphs for each drug substance, i.e., the active pharmaceutical ingredient, need to be identified and quantified before the commercial use of drug substances. The characterization and quantification of each phase in a sample have enabled even a precise diagnosis of diseases such as urolithiasis and a prophylaxis, 1 an estimation of the lixiviation performance of the host for radioactive elements, 2 and the deciphering of the magma mixing phenomena.…”

“…3 Consequently, many studies have quantified solid-state structures and phases by various spectroscopic methods. [1][2][3][4][5][6][7][8][9][10][11][12] However, powder sample mixing to obtain calibration curves and to apply a standard addition method 9 causes significant variance in the quantification of solid-state phases, in contrast to liquid samples, due to the difficulty in ensuring a homogeneous mixing of solid-state polycrystalline powders. Especially with limited sample amounts, a larger error may be produced due to the presence of remnants on the surface of mixing tools.…”