Monitoring daily routine performance in quantitative NMR (qNMR) spectroscopy: Is the system suitability test necessary?

Abstract

Nuclear magnetic resonance spectrometry (NMR) finds numerous applications in pharmacy, cosmetic, and food control as well as in developing tools for “big data” analysis. However, there remains a need for automated tools to assess instrument system suitability in real time for each particular routine sample. An automated procedure has been introduced to monitor a number of characteristics (resolution, symmetry, and half width) in real time after the measurement of two samples distributed by the vendor (0.3% CHCl3 in acetone‐d6 with tetramethylsilane and 2 mM sucrose in H2O‐D2O). The results over 11 months were discussed in terms of average values, standard deviations, and spectrometer variability. Moreover, multivariate statistical procedure was implemented to evaluate metrics generated from three NMR spectrometers. Performance of three NMR spectrometers (500 MHz with BBO Prodigy Cryoprobe, 500 MHz with BBFOPLUS SmartProbe, and 600 MHz with BBO Cryoprobe) differed significantly. The developed routine was also applied to calculate the performance characteristics during routine quantitative NMR experiments. The procedure was evaluated for NMR spectra of 659 active pharmaceutical ingredients dissolved in CDCl3, DMSO, and CH3OD. This test is more preferable than the routine procedure using standard solutions because the performance is estimated separately for each matrix at the specific time point of measurements. Our automated routine is the ideal tool for any NMR laboratory. In full automation, the NMR data are validated directly for each sample, making unnecessary daily measurements of standard solutions and manual evaluation to their NMR spectra.

A Step Towards Optimization of the qNMR Workflow: Proficiency Testing Exercise at an GxP-Accredited Laboratory

“…For automated NMR spectra evaluation, a macro was written within the NMR Bruker software, which connects previously developed Matlab script and the Topspin environment [6][7][8]. For spectra evaluation, only integral borders and the center of the signals have to be defined manually by an operator.…”

“…Our routine checks the presence of phase and baseline distortions as well as unrelated resonates in the analyte region. Further details can be found in our previous publications [6][7][8].…”

“…On the other side, data analysis is another crucial part of the qNMR workflow. A tool for automated integration in qNMR analysis has been recently developed, which helps to prevent transfer errors during data evaluation, identify spectral artefacts, and enables high throughput of the whole analysis workflow [6][7][8]. This routine also verifies preprocessing and integration steps in a fully automated manner.…”

“…This routine also verifies preprocessing and integration steps in a fully automated manner. The approach was successfully tested on binary mixtures of qNMR internal standards having simple spectra, as well as complex multiplet patterns of pharmaceutical products [6][7][8]. It was hypothesized that our user-independent procedure can be used to check the quality of quantitative results.…”