Method Performance and Validation for Quantitative Analysis by ¹H and ³¹P NMR Spectroscopy. Applications to Analytical Standards and Agricultural Chemicals

Abstract

Nuclear magnetic resonance (NMR) can be used to provide an independent and intrinsically reliable determination of chemical purity. Unlike chromatography, it is possible to employ a universal reference standard as an internal standard for the majority of chemical products assayed by quantitative NMR (QNMR). This is possible because the NMR response can be made the same for all chemical components, including the internal standard, by optimizing certain instrumental parameters. Experiments were performed to validate the quantitative NMR method described in this paper for the analysis of organic chemicals. Experimental precision, accuracy, specificity, linearity, limits of detection and quantitation, and ruggedness were systematically addressed, and system suitability criteria were established. The level of the major chemical ingredient can be determined with accuracy and precision significantly better than 1%, and impurities may be quantified at the 0.1% level or below. Thus, QNMR rivals chromatography in sensitivity, speed, precision, and accuracy, while avoiding the need for a reference standard for each analyte. Examples are given of (1)H and (31)P NMR used for quantitative analysis of agricultural chemicals, and a method for characterization of analytical standards is presented.

Purity analysis of hydrogen cyanide, cyanogen chloride and phosgene by quantitative 13C NMR spectroscopy

“…Maniara et al 21 reported a systematic validation of the quantitative NMR method. Their validation demonstrated that when carefully implemented, the purity of major components in a complex mixture can be determined with accuracy and precision better than 1%, and impurities comprising Ä0.1% of the sample mass can be quantified.…”

Quantitative Analysis of Cannabinoids from Cannabis sativa Using 1H-NMR

“…The usefulness of quantitative NMR for the validation of natural product reference compounds as well as theoretical aspects have been shown by Maniara and Pauli. 13,14) The developed method was applied on the quantitative analysis of five different isolated cannabinoids. A similar method has been recently described by our laboratory for the quantitative analysis of bilobalide and ginkgolides in Ginkgo biloba leaves and products.…”

Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol

“…Considering the excellent localization properties of the LASER-FOCI sequence [24], as confirmed herein, the phantom results of the protocol compare well with other assays. Yet, the LMRS protocol is roughly three times less accurate than high-resolution, non-localized MRS assays [34,35]. Though some decrease in accuracy results from low analyte-to-reference ratios, it is primarily attributable to larger line widths and gradient-induced spectral noise, as is well known.…”

“…3 suggest that the adiabatic sequence correctly assays the voxel. With regard to concentration, the linearity of the MRS response to the number of nuclei is well documented [34,35]. The LMRS response of the protocol is the relaxation corrected analyte-to-reference ratio of the integrated intensities, S 0 .…”