Evaluation for Standardization of ¹H Quantitative NMR Spectroscopy by Round Robin Test

Abstract

 ¹H quantitative NMR (¹H qNMR) is known as a powerful tool for determination of analytes without the need for their identical standards, which is eligible to a primary rate method. ¹H qNMR has been already stipulated to an assay for purity determination in Japanese Pharmacopoeia (JP), and then this technique has been also applied in several fields such as pharmaceutical and food sciences. However, there is little information about the accuracy of ¹H qNMR so that the further applications into other fields such as industrial chemistry could be constricted. In this study, in order to assess the reliability of ¹H qNMR, we designed the round-robin test of ¹H qNMR under the basis of the measurement conditions described in JP. 1,4-Bis(trimethylsilyl)benzene-d₄ [1,4-BTMSB-d₄, 99.9±0.6% (w/w)] and 3,5-bis(trifluoromethyl)benzoic acid [3,5-BTMFBA, 99.96±0.06% (w/w)], which are certified reference materials (CRMs), were adopted to analyte and qNMR reference standard respectively for the accurate evaluation in this test. Six NMR instruments in 5 institutions optimized to ¹H qNMR conditions provided the purity 1,4-BTMSB-d₄ within acceptable error range. This result represented that ¹H qNMR has the capability to determine precisely the value of analyte in practical analytical field and to be set as official analytical method for purity determination or assay of concentration of organic compounds.