Takako Suematsu

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

 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.

Analytical Standards Purity Determination Using Quantitative Nuclear Magnetic Resonance

Quantitative nuclear magnetic resonance (qNMR) with Internal Standard named as AQARI (Accurate QuAntitative NMR with Internal standard material) has been adopted by the Japanese Pharmacopoeia and the Japanese Standard of Food Additives as an official analytical method because of reliability and efficiency. We have developed Certified Reference Material (CRM) suitable for AQARI and utilitized AQARI with developed CRM to characterize analytical standards and certified reference materials (CRMs) for use in developing qNMR and chromatographic calibration standards. AQARI was used to determine the chemical purity of analytical standards for more than 500 compounds, including the following seven Japanese Pharmacopoeia crude drug products: magnolol, geniposide, paeonol, magnoflorine Iodide, saikosaponin b2, (E)-cinnamic acid and rosmarinic acid.